Steroids in Uveitis

2007Steroids in Uveitis

uveitisJournal of the Uveitis Information Group | 2 £

Uveitis_uk_040907 05.09.2007 10:45 Uhr Seite 1

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Editorial

“Steroids are horrible!!” “Steroids are ruining my body!” Nearly everypatient with uveitis has got her or his experience with “steroids”. In case ofmild anterior uveitis, topical treatment with drops or ointment probablycauses no problems. Unfortunately, more severe forms, but also most ofthe intermediate and posterior forms of uveitis, are not effectively treatedby topical steroids. Often patients find their individual side effects. So,there are a whole bunch of questions and misunderstandings surroundingthis drug. This edition of uuvveeiittiiss will help to increase your knowledge aboutsteroids: How do they work? What kind of topical steroids are available inEurope? We will learn that the side effects of steroids mostly depend on theform they are applied, the duration of treatment and the intensity. What arethe side effects, how can we avoid them? We also will clarify when steroidsshould be substituted by immunosuppressives. Children especially are verysensitive to long–term steroid treatment, which tends to lead to an earlierstart of immunosuppressive treatment.In most uveitis patients steroids are unavoidable but the physician shouldalways try to discontinue this treatment or limit it to a tolerableminimal dosage.Finally we will conclude this issue with the views of 3 people, involvedin this treatment: “Thoughts about Steroid Treatment for Uveitis” willsummarize the experience of an Ophthalmologist, an ophthalmic nurseand a uveitis patient. We hope that all readers can find usable informationfor their future steroid treatment from this journal.How was uveitis treated, before in the 50´s of the last century steroidsentered ophthalmology? We look back to 1910, when Dr. Andrew Wilsonsummarized his knowledge about this disease.Since 2003 the German Patient Interest Group (DUAG) has provided 6awards for uveitis research. Various studies show that useful drugs, whichwere under investigation, have already found their way into moderntreatment principles. Last years awards will be described in detail here.

Manfred Zierhut,Professor of Ophthalmology, University Eye Clinic of Tübingen,Germany, august 2007


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Content

Patient Groups & Information . Imprint

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Patients – Two patients report on their Experiences with SteroidTreatment Today, patients from Italy and Germany describe their story aboutthe positive and negative feelings under steroid treatment.

News from the Scientific World – Uveitis Awards of the GermanPatient Interest Group (DUAG) 2005 In 2005 for the third time, theDUAG has provided 6 awards for clinical and experimental uveitis research.This report describes the award finding process and the content of theawarded work.

P. 54Cover Picture - Nan Mulder, UK

P. 14 Periocular and Intraocular Steroid Treatment Besides severe forms ofanterior uveitis, all inflammation of the posterior segment of the eye will needa higher dosage of steroids, which can be applied by injection around theeye or even inside. Recently also a steroid releasing device has reachedophthalmology. All you should know about these will be reported byProf. Carlos Pavesio from London.

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Side Effects of Corticosteroids Unwanted effects may be encounteredwith steroid therapy. Prof. Ilknur Tugal-Tutkun from Istanbul, Turkey, willsummarize what we have to be aware of when using steroids for uveitis.

P. 5 History and Effects of Corticosteroids This edition about “Steroids” willstart with some historical remarks by Prof. Antonio Secchi, Padua, Italy,followed by explanations about the effect of steroids on general and ocularinflammation.

P. 51 Cultural Corner – A Look back into 1910 Uveitis is not a new disease,and Phil Hibbert reports about the amazing knowledge about this disorderapp. 100 years ago.

P. 9 Steroid Eye Drops The first drugs for an effective treatment of anterioruveitis are steroid drops or ointment. Pierre-Yves Robert, ophthalmologist inLimoges, France, will describe what you should know about the variousformulations.

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Use of Corticosteroids in Children with Uveitis Probably the mostchallenging group of uveitis patients are children. Prof. Arnd Heiligenhaus andCarsten Heinz, Uveitis Center in Münster, Germany, will summarize theupdated concept for a steroid therapy in these children, but also its limitation.

P. 27 Thoughts about Steroid Treatment for Uveitis Different peoplemay have completely different impressions about steroid treatment. We haveasked a patient, an ophthalmic nurse and an ophthalmologist.


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symptoms and signs of the disease. Ittook several decades to find out that thisstatement was not completely true:steroids can also cure an inflammatorycondition whose pathogenesis is most-ly related to immunological events( = immunosuppressive effect ), al-though perhaps more often they areused (incorrectly? correctly? we mightspend weeks on this debate, withoutreaching a safe conclusion) only assymptomatic drugs. It depends mostlyon how much and how long the drug isused: low dosages for a short time willlikely have only a symptomatic effect.

Steroids and OcularDiseasesIn the very middle of the 20th centurysteroids became available in thearmamentarium of all physicians trea-ting inflammatory diseases and, on this

How the Steroid StorybeganRheumatoid arthritis, to name one ofthe most significant and frequentclinical conditions in this area, changedits often dramatic clinical coursesubstantially when, in 1949, steroids ofthe first generation became available onthe market. Side effects were oftenimportant, sometimes very important,but the general outcome of the diseasebecame in a very short time quitedifferent after this new treatment, muchbetter than what both physicians andpatients were used to experiencing untila few years before. Other inflammatorydiseases beside rheumatoid arthritisbegan to be treated with the new drugs,generally with good results, although akind of “be careful!” approach soonbecame apparent: it seemed thatsteroids do not really influence thecause of the disease; they simply reduce,to a different extent in different clini-cal conditions, the severity of both

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History and Effects ofCorticosteroidsThere is no doubt that, in the history of medicine, few drugs changed both diseases’course and patients’ lives to the extent that steroids did in inflammatory diseases.Prof. Antonio Secchi, Head of the Department of Ophthalmology at the Universityof Padua, Italy, invites you to a short journey into the history of the developmentof steroids, and he also will describe how steroids affect inflammation.


occasion at least, ophthalmologists wereamong the first to use the newtherapeutic opportunity. It was at thebeginning of the ’50s, in fact, that topi-cal preparations of hydrocortisone be-gan to show up on the druggist’sshelves, and both systemic and topicalsteroids began to be used also ininflammatory diseases of the eye.In the second half of the century thephysiological evolution of pharmacology(searching for stronger drugs with loweror even no side effects) involved alsosteroids, and generation after generationof new drugs appeared on the market.Since it should be understood that a“new” drug does not necessarily implyto be a “better” drug as well, a fewpoints need to be clarified.

What should we expect bythe Use of Steroids in ocularInflammation?The aims for the steroid treatment canbe the following ones: a fast resolutionof the signs, minimal, or, even better, nocomplications related to the inflam-mation; a longer interval between(possible) relapses of the disease; few,manageable, or no side effects.How can these goals be reached?Answering in the most proper way –which is often different in the differentclinical conditions, and may be differentamong different patients showing thesame clinical condition – a panel of

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other questions come up: when shouldthe therapy be started? Which steroidshould be used? How: topical, systemic,parabulbar, intraocular? How much?How long?The answer to “when” should be: soonenough. When the ophthalmologist has“decided” that “this” specific conditionrequires the use of steroids, there isusually no reason for postponing thetreatment. This “decision”, however,must be sound and thoroughlyevaluated in advance in each case.Steroids should only be used when othertreatment, likely to be less dangerous inview of the steroids’ known side effects,would be anticipated not to behaveeffectively enough in that clinical con-dition. It is not a simple decision.

The Problem of Side EffectsAt times the (future) price to pay for anadequate use of steroids – in terms ofside effects, which may be minimizedbut almost never avoided – may be toohigh given the real severity (in the longterm) of the disease to be treated. Druginduced complications, in other words,may be more severe than the diseaseitself. Several subcategories of uveitis, infact, are certainly annoying for thepatient, but not so really severe tobalance the risk of a chronic treatmentwith steroids. To decide whether to start,or not, a steroid treatment is certainlyone of the most important points in the


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road map of inflammation in general,and of uveitis in particular. Lots ofknowledge and specific experience arerequired for a sound decision from thedoctor’s part. Lots of understanding andpatience must be exerted by the patient.Good sense and feedback/interactionmust exist for a positive and rewardingrelationship between the two partners.

Which Steroid should beused?Latest generation preparations areoften thought (sometimes only hoped)to have lesser systemic effects, but notnecessarily to be considered “better”.“Deflazacort”, to name one of the recentdrugs, is thought to be less dangerousthan prednisone in terms of side effects.The latter’s efficacy, however, isconsidered by many colleagues to besubstantially stronger. So, given thatequivalent (again not such a simpleissue) doses of different steroids shouldgive a similar anti-inflammatory effect,the Ophthalmologist should try tobecome fully acquainted with a fewpreparations, and use them in themajority of his/her cases.

How should Steroids beapplied?The topical application of steroids is themost effective way. This includes para-bulbar, subconjunctivally and (onlywhen strictly required) intravitreal

injections. Intravenous application isindicated, when the effect required isnecessarily urgent. Orally in most casesof chronic treatment, with a prolonged,slow tapering.

How much Steroid shouldbe used?Again, the answer should be: enough.The writer of these lines is stronglyconvinced that many cases of chro-nicization of inflammatory diseases likeuveitis are due, at least partially, totreatment often not adequate at thebeginning of the disease. Too littlecortison, for a short time, with atapering too fast, may result in an“apparent” healing of the disease, whichwill “resurface” after a short interval,and slowly become chronic.That is the main reason why thedecision of starting steroids as a therapyshould be weighed very carefully. If thedecision is “yes”, the initial amount ofdrug, the length of the treatment, theslowness of tapering must be adequate.If not adequate, a relapse of theinflammation will be very often only amatter of time, and chronicization willlikely follow.

How long should Steroidsbe used?This is probably the most difficultquestion to answer, and the usualsuggestion of going ahead with the


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therapy for at least two months withoutinflammatory signs, must be taken forwhat it is: just a suggestion.

How do these Drugs work?An extensive answer to this questioncould be very complicated. Generallyspeaking, inflammation is the result ofa net of interactions which eventuallylead to an extensive damage of cellmembrane permeability. Two thousandyears ago the Romans had already clearideas on the matter: inflammation ismade of

tumor:swelling, due to an effusion of fluidsfrom hyperpermeable vessels,

rubor and calor:hyperemia and heat, due to vasodilation,

dolor:pain, not a common symptom in uveitis,although often present in inflammationas due to a stimulation of dedicatedreceptors, and lastly

functio lesa:damage to sensible targets made by(often relapsing) inflammatory phe-nomena.Steroids do limit or block theappearance at the inflammation sitesof the chemical mediators (mostly“cytokines”) which make the net ofinteractions start, or get itself going in arelapsing or in a continuous, chronicway. This effect is obtained through the

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inactivation of specific cells (amongstothers macrophages, monocytes,lymphocytes, leukocytes, fibroblasts,endothelial cells), which are responsiblefor the formation and activation of thespecific mediators. Steroids turn off, invery few words, a switch that theinflammatory agent had turned oninitially – or that will be turned on againto trigger a relapse of inflammation. Theinflammation will subside if the treat-ment was carried out properly in termsof “which steroid”, “how”, “how much”and “how long” – without, or withminimal damage if the therapy wasstarted soon enough. The signs and thesymptoms of inflammation will, on thecontrary, relapse if the treatment wasnot adequate in terms of timing, do-sage, length, tapering.

ConclusionIt is the doctor’s responsibility, and thepatient’s as well when it comes tocompliance, to use when necessarythese powerful drugs called steroids inthe most proper and effective way. Theymay do “miracles”, only if thoroughlyknown, and used in each case with theconfidence and the respect they actuallydeserve.


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Steroid Eye DropsThe first step for an effective treatment of anterior uveitis is topically applied steroiddrops. Twenty years ago, steroid eye drops were the only treatment for a number ofeye diseases. In this article, Pierre -Yves Robert, ophthalmologist from Limoges,France, describes the differences between the various steroid drugs, their mainindications, and how they should be applied to the eye.

Are all Steroid Eye Dropsthe same?Seven steroid molecules have beencommercialized to date, some of themin combination with an antibiotic. Theydiffer regarding their anti-inflammatoryeffect (depends on the type of steroid)and regarding their ability to penetratethe cornea (depends on the chemistry).hydrocortisone and prednisolone(which have the lowest anti-inflammatory action), dexamethasone(which has the highest), fluoro-metholone and rimexolone (with lessinfluence on intraocular pressure due tominor corneal penetration), and twoderived molecules, loteprednol etabo-nate and medrysone. The difference intheir chemistry leads to a differentuptake through the cornea, whichinduces various degrees of elevation ofthe intraocular pressure, one of themost important side effects.

When are Steroid Dropsindicated in Uveitis?Local steroid therapy is the standardtreatment of every acute anteriorintraocular inflammation (Figure 1 ). Inthis case a steroid, which penetrates thecornea well, e.g. dexamethasone or pred-nisolone, will be applied. The frequencycan reach once an hour, sometimes evena frequency of each half an hour can beindicated. Dose and duration have to be

Figure 1:Acute anterior uveitis with inflam-matory precipitates on the backside ofthe cornea (endothelium)


adapted to the course of intraocularinflammation and to eventual sideeffects. Unfortunately, topical steroidscan not reach high concentrations inthe vitreous or at the retina. So, in casesof intermediate and posterior uveitisthey are only used, when additionallyinflammatory cells are found in theanterior chamber.

Are there Side Effects whentopical Steroid Drops areused?The side effects of topically appliedsteroids depend on the dosage and thetime they will be applied. The majorside effects in the eye are glaucomaand cataract induction.

Steroid-related GlaucomaSteroids can raise the intraocularpressure (IOP). A 5mmHg raise iscommon in young patients after 3weeks of treatment and can be foundin app. 30% of people. This effect isespecially noted after local treatments(eye drops, parabulbar or subconjunc-tival injections). Steroid-related glau-coma develops when this IOP raisesmore, but it is impossible to predict itsdelay and seriousness, which can startafter a few days or a few months afterthe beginning of steroid treatment. Thereason for the elevation of the pressureproblem is found in the outflow systemof the eye, the so-called “trabeculum

Figure 2:Cataract, induced by steroids

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meshwork”. There, newly formed sub-stances, glucosaminoglycans, fill thegaps, which normally are used for theaqueous humor to leave the anteriorchamber. Therefore, prophylaxis ofsteroid-related glaucoma relies on astrict follow up of IOP in long-termsteroid treated patients. This effect islower with steroids as fluorometholoneor rimexolone, which poorly penetratethe anterior chamber.Nevertheless, these molecules caninduce steroid-related glaucoma too,and the same follow-up of IOP ismandatory.

Steroid- related CataractLong-term steroid therapy induces atypical posterior capsule opacification(Figure 2 ) in 30% to 40% of patientswho receive 10mg prednisone during

2 years. This climbs up to almost 100%after 4 years. Specific receptors in lens


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epithelial cells and the susceptibility ofthese cells to steroids are responsible forthe development of lens opacifications.

Corneal Epithelium Toxicityand InfectionAfter some time steroid eye drops mayweaken corneal epithelium and maypromote corneal infections which canresult in ulceration. In children, theymay thin corneal stroma up to cornealperforation, especially in long-termtreatments.

ContraindicationsThe essential contraindications ofsteroid eye drops are acute infections ofthe ocular surface. Viral (especiallyacute herpetic, Figure 3), fungal, acantha-moeba or bacterial infection that is notunder control, is a contraindication forlocal steroids. For this reason, pres-cribing steroid eye drops should bereserved to ophthalmologists.

Figure 3:Keratitis, due to herpes simplex virusinfection.

ConclusionIf the inflammation of the eye is locatedin the anterior part of the eye, localsteroid drops are the first line oftreatment. The advantage of this treat-ment is that they reduce ocularinflammation very quickly, withoutsystemic side effects. But used fre-quently (e. g. every hour) they alsocan lead to a remarkable steroid con-centration in the blood. Their use islimited due to side effects like cataractformation and elevation of the intra-ocular pressure. So, even topical steroiddrugs have to be used carefully andfor a defined time.

The following table lists steroid eyedrops and ointment, available in someEuropean countries and the USA.


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France

Germany

UnitedKingdom

Italy

Netherlands

USA

Hydrocortisone

FicortrilHydrocortisone POS

Hydrocortisone

Prednisolone

Solucort ophta

Inflanefran fortePredni-ophPrednisolone-

JenapharmPredni-POSUltracortenol

PredsolPredsol NPrednisolone

Pred forteUltracortenolPrednisolon

AK-PredEconopredEconopred PlusInflamase ForteInflamase MildPred FortePred MildPrednisolPrednisolone oph

Fluorometholone

Flucon

EfflumidexFluoroposFluoro-Ophtal

FML

FlarexFluatonFlumetol semplice

FML LiquifilmFlarex

FlarexFluorometholone ophFML LiquifilmFluor-OpFML S.O.P.FML Forte LiquifilmEflone

Table: Steroid eye drops available in France, Germany, United Kingdom, Italy, Netherlands


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Dexamethasone

Maxidex

Dexa-EDSDexamethason-

JenapharmDexapos, DexagelDexa-sine SEIsopto-Dex, SpersadexTotocortin

Maxidex

EtacortilenLuxazoneVisumetazone

Dexamethason

MaxidexDexamethason

AK-DexDecadron OcumeterDexasolMaxidexDexamethason oph

Rimexolone

Vexol

Vexol

Vexol

Vexol

VexolRimexolone oph

Loteprednoletabonate

Lotemax

Lotemax

AlrexLotemax

Medrysone

Medrysone ophHMS

and U.S.A.


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What are the Modalitiesof local Treatment in Uveitisaffecting the Back of theEye?This form of treatment involves the useof either injections of steroids, whichcan be delivered around the eye ordirectly inside the eye, or the use of adevice (implant), which is surgicallyimplanted inside the eye and will deliverthe medication over a prolonged periodof time.There are two types of injectionsaround the eye: the orbital floor in-jection (Figure 1 ), which delivers themedication a bit further away from theeyeball, and the posterior sub-Tenon’sinjection (Figure 2 ), which puts thedrug very close to the back of the eye.In both cases the drug will penetrateinto the eye by moving through the wallof the eye, called sclera, and reachingthe place where the inflammation istaking place inside the eye. However,

the sclera represents a barrier and willlimit how much of the medication getsinside the eye.To bypass this barrier the medicationcan be put directly inside the eye, andthis can be done by an injection or bythe device mentioned above. The in-jection will go through the sclera (eyewall) and put the drug in the posteriorcompartment of the eye, filled by a gel-like substance, called the vitreous body(Figure 3 ). The device is implanted by asurgical procedure, which will create asmall cut in the sclera and will insert thedevice into the eye, anchoring it to theeye wall (Figure 4 ).

When should this Form ofTherapy be considered andwhen not?These options should be considered ifthe uveitis is affecting only one eye, or ismuch more serious in one of the eyes,

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Periocular and IntraocularSteroid TreatmentUveitis which involves the anterior part of the eye can be treated with the use ofsteroid eye drops, but when the back of the eye is involved drops don’t penetratedeep enough to treat the inflammation. The use of oral medication is often necessaryto treat this posterior type of the disease, but in some situations local treatment isstill a good alternative. Prof. Carlos Pavesio who works at the Moorfields Eye Hospitalin London, UK, describes the indications and limitations of corticosteroid injectionsaround or inside the eye.


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but also, when other medical problemsexist which contraindicate the use of oraltreatment, such as poor controlleddiabetes or high blood pressure, andalso stomach ulcers or if severe

Figure 1 :Orbital Floor Injection

Figure 2 :Posterior Sub-Tenon´s Injection

Figure 3 :Intravitreal Injection

Figure 4 :Implantation of a Steroid Device intothe vitreous

psychological problems like a psychosishad developed under the use ofcorticosteroids before. Local therapywith steroids should be avoided inuveitis caused by an infection and also if


acting, while others are considered adepo (deposit). Both are used forperiocular injections, but for intra-ocular injections the long-acting form(triamcinolone) is the one currentlyused. These formulations will allowduration of the effect of about 4 months.The implanted device uses a differentsteroid (fluocinolone acetonide) andhas been designed to release the drugover a period of 2.5 years.When the effect is over and the diseasestill active, which is the case in mostpatients, another injection, or a newdevice will be needed.

What happens when theydon’t work?Periocular injections may take a fewweeks to become effective, but if theydon’t work after 4 weeks, the doctorwill probably decide to repeat it. Onlyafter a second or even third failure theprocedure should be abandoned andother alternatives sought. Intraocularinjections usually work very quickly(about 1 week) and if they fail it mayindicate that the problem is very seriouswith permanent damage and no benefitin trying other forms of therapy maybe expected.Devices are implanted only afterevidence of response to steroids isavailable, and they tend to work wellfor the full duration of the treatment(2.5 years). Relapses of the disease maystill occur with the implant, but

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you already have a problem with highpressure in your eye.

How are these Treatmentsgiven?The periocular injections are givenunder local anaesthesia and procedurescan be carried out in the officeenvironment. The intraocular injectionneeds a sterile environment (a separateroom) and a well-defined standardprocedure to minimize the risk of aninfection. It is also given under localanaesthetic. The intraocular device isinserted in the operating theatre underlocal or general anaesthesia.

What happens after theProcedures, how long doesthe Effect last and whathappens when the Effectis over?In any case the patient should be ableto go home on the same day and youwill be given a prescription for anantibiotic eye drop to be used for a fewdays. All other medications normallyshould be continued and the doctorwill give instructions about how tostart reducing them later. There shouldbe a control appointment for a reviewvisit in a short time.For the injections, the duration of theeffect depends on the type of steroidformulation used. There are somesteroids which are considered long-

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they are much less common whencomparing to oral therapy. If the deviceis not achieving the desired effect, andespecially if it is causing problems(pressure rise), it can be removed.

What are the potentialComplications of theseTreatments?Some complications are related to theprocedure (injection or implant) itself,while others will be due to the localeffect of the steroid drug. During anyinjection or surgery complications canoccur and they vary from simple onessuch as haemorrhages, which may leaveyou with a black eye for a short time (inperiocular injections), to more seriousones such as infections (in intraocularprocedures), which, to mention theworst outcome, may result in loss ofvision. Probably the most commoncomplication for periocular injections isa droopy upper lid (ptosis). This tendsto disappear within days of the injec-tion, but rarely it may last longer ornot reverse without surgery.

For the intraocular procedures thereare also some long term potentialproblems, especially the appearance ofcataract and elevation of the intraocu-lar pressure.Unfortunately after intraocular in-jections cataracts often progress andneed surgery. The removing procedure

itself usually does not represent aproblem, but may become a problemin young patients for whom a func-tioning clear lens is very important.High pressure may lead to glaucomaand the management involves eyedropsand sometimes surgery. It should bestressed that cataract and glaucoma arealso not uncommon complications ofuncontrolled uveitis.It is also important to remember thateven though the complications men-tioned above may occur, the in-flammation needs to be controlled or itwill result in even more severe damageto the eye.

ConclusionPeriocular, and more recently intra-ocular corticosteroids are very helpfulways to supply the uveitic eye withcorticosteroids and to avoid majororganic side effects, compared tosystemic application. New types ofcorticosteroids are being developedwhich may be effective in the treatmentof uveitis, but at the moment they areavailable only for undergoing studiesand not commercially available. Theywill very likely represent new alterna-tives for the future.


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Side Effects of CorticosteroidsThe corticosteroid preparations used by the physician are modified derivatives ofthe natural glucocorticoid hormones produced in the body. Given the multitudeof organ systems targeted by these hormones, widespread unwanted effects may beencountered with corticosteroid therapy. The severity of these side effects depends onthe dose and duration of treatment. Ilknur Tugal-Tutkun, Professor for Ophthalmologyat the University of Istanbul, Turkey, introduces the organs which can be affectedduring corticosteroid therapy in various ways.

Adrenal SuppressionHigh-dose long-term corticosteroidtherapy inhibits production of nativehormones. In cases of stress, such asmajor injury, infection, or surgery, thebody’s inability to rapidly produceadrenal corticosteroids may cause severeillness. Patients must inform anytreating physician of their past orpresent corticosteroid therapy becausecorticosteroids should be reintroducedor the dose should be increased in acutestress. Too rapid tapering or suddendiscontinuation of corticosteroids mayresult in a withdrawal syndromecharacterized by symptoms, includingmalaise, muscle and joint pains, lossof appetite, and anxiety.

Fluid Retention, ElectrolyteImbalance, and Hyper-tensionFluid and sodium retention may causeedema, that is painless swelling ofespecially lower legs, ankles, and feet.

This side effect can be reduced by a lowsalt diet. A diet rich in potassium isrecommended, in order to compensatefor potassium loss. The blood pressureshould be checked on a regular basis.Congestive heart failure may develop inpatients who have an increased risk.

Endocrine and metabolicAbnormalitiesRedistribution of body fat results in aclassical appearance called “Cushingoidstate” which is characterized by moonface (puffing of face), buffalo hump (alump of fat on the back of the neck),upper body obesity, and thinning of thearms and legs. Some individuals aremore prone to develop this appear-ance than others. Serum lipids, bothtriglycerides and cholesterol, may beincreased. Because weight gain can beenormous in some patients, a calory-controlled diet is recommended. Thismay also reduce the risk of developingdiabetes.


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Figure :Various organs can become influenced under steroid-treatment


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Corticosteroids can cause a change inglucose tolerance and an increase ofblood glucose level by 10 -20 %.Increased thirst and frequent urinationmay be early symptoms. Diabetic pa-tients must be aware that their bloodglucose level, because it may deteriorateduring corticosteroid therapy and thatthey may need an increased antidiabetictreatment. Sex hormones are reducedand menstrual irregularities andamenorrhea (stop of the monthlybleeding) can occur during cortico-steroid therapy.

Gastrointestinal DisordersGastrointestinal side effects of cortico-steroids include increased appetite,indigestion, nausea, gastritis, stomachulcer, bowel perforations, and rarelypancreatitis. A past history of pepticulcer, smoking, alcohol consumption,and the use of other ulcerogenic drugssuch as nonsteroidal anti-inflammatoryagents are risk factors, and such pa-tients require prophylactic treatmentwhen corticosteroids are administered.

OsteoporosisLong-term corticosteroid therapy causesthinning of the bones and an increasedrisk of fractures. Elderly patients,postmenopausal women, smokers, andpatients with limited mobility have anincreased risk. Bone densitometry is anobjective method of measuring bonemineral density and should be

performed at the initiation of cortico-steroid therapy and annually thereafter,especially in the high-risk group.Calcium and vitamin D supplementsmay be recommended for prevention ofbone loss. Anti-resorptive medicationsand hormones may be prescribed for thetreatment of osteoporosis. Bisphos-phonates are the only acceptedprophylaxis for steroid-induced osteo-porosis and should be used in allhigh-risk individuals from the be-ginning of therapy and for all otherpatients who develop osteopenia.

OsteonecrosisAlso known as avascular or asepticnecrosis of the bones, this is a seriousbut rare complication of corticosteroidtherapy. Head of the thigh bone (hipjoint) is most frequently involved, butother large joints may also be affected.Joint pain and stiffness are the earliestsymptoms. Early diagnosis is importantin order to prevent further deterioration,because total joint replacement withprosthesis is the only definitive treat-ment when irreversible joint destruc-tion develops.

Growth RetardationIn children, corticosteroids inhibit longbone growth. Alternate day treatmentmay reduce this risk and discon-tinuation of corticosteroids may allowchildren to catch up their originalgrowth rate.


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MyopathyMuscle weakness and loss of bulk ofespecially the shoulder muscles andthighs can occur because of a reductionof protein synthesis. Potassium loss mayalso cause muscle weakness. Musclecramps, pain, and weakness may limitmobility. Recovery of muscle weaknessmay be slow and incomplete even afterdiscontinuation of corticosteroids.

Neurological and psychiatricDisturbancesOnset of headache may be a symptomof increased intracranial pressureassociated with corticosteroid therapy.Trouble in sleeping, mood swings, afalse sense of well-being, excitement,restlessness, hallucinations, aggression,depression, and suicidal attempts mayall occur even in individuals without anyprevious psychiatric problems. Patientsand their families should be informedabout these potential side effects whenhigh-dose corticosteroid therapy isadministered. Steroids are contraindi-cated in the presence of a psychiatricdisturbance caused by previous ex-posure to the medication.

Skin ChangesIncreased sweating, darkening of skincolor, facial rash, thin shiny skin, easybruising, hair loss, hirsutism (unwantedhair growth), poor wound healing, acne,and stretch marks (reddish purple lineson arms, legs, and trunk) are thedermatological complications of cor-ticosteroid therapy.

Suppression of the immuneSystemCorticosteroid use is associated with anincreased susceptibility to infections.Because severity of the infection may bemasked, patients should seek medicalattention even for mild symptoms thatmay suggest an infectious disease.

Ocular side EffectsLong-term systemic corticosteroidtherapy may cause cataract and glau-coma (optic nerve damage associatedwith increased intraocular pressure).

ConclusionFortunately the most severe side effectsare noticed only after long standinguse of corticosteroids. It is mandatoryto ask the patient, but also for the pa-tient to inform the treating doctor aboutthe side effects. Some of these effectscan be avoided.


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Use of Corticosteroids inChildren with UveitisThe probably most challenging group of uveitis patients are children who developsome of the most treatment resistant forms of uveitis. Even for them corticosteroidsare the first choice of treatment. Prof. Arnd Heiligenhaus and Carsten Heinz, bothworking at the Uveitis Center of the St. Franziskus Hospital in Münster, Germany,summarize what is important to know about corticosteroids in children.

Endogenous Uveitis inChildhoodUveitis in childhood is less commonthan in adults. It may appear in variousinfectious and non-infectious (endo-genous) forms and is classified an-atomically as anterior, intermediate,posterior and panuveitis. The mostcommon form is anterior uveitis.Uveitis in childhood may be associatedwith a systemic immune-mediateddisease, and the most important entitiesare juvenile idiopathic arthritis (JIA)and ankylosing spondylitis.

Corticosteroids as firstChoice Medication forUveitis in ChildhoodIndependent of the patient age, themajor goal in the treatment of uveitis isimprovement or preservation of visionand protection from vision threateningcomplications. In the acute phase of theattack, a reduction of inflammation is

attempted. Thereafter, recurrence andchronic inflammation must be avoided.

Even in children, corticosteroids are thefirst choice medications for treatment.Profound clinical and experimental datashow that they are highly effective toreduce inflammatory activity of uveitis.Favorably, the anti-inflammatory effectof corticosteroids begins soon afterstarting the treatment.

General Remarks aboutCorticosteroid Use inUveitis in ChildhoodNo general guidelines are provided forthe use of corticosteroids, with theexception that the dosage of topicalcorticosteroids should be adjusted to thenumber of cells in the anterior chamber.Generally, complete abolition of anycells in the anterior chamber isattempted. Corticosteroid dosages,frequency and intervals of application

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and length of therapy may differmarkedly between the patients. Thetreatment regiment must be adjusted tothe anatomic type and course of uveitis,the complications and associatedsystemic immune-mediated disease.The route of application, dosage andduration of corticosteroid applicationmust be adapted to the individualcourse of uveitis.

Corticosteroids can be usedby various ApplicationRoutesCorticosteroids may be used in variousformulations. High dosages in theanterior chamber can be obtained witheye drops, gels or ointment. In child-hood, eye drops are preferentially givenduring the day to avoid visualimpairment and subsequent amblyopia.Dexamethasone 0.1% and prednisoloneacetate 1% are favored due to their highanti-inflammatory potency. Ointmentmay be preferred at bedtime.

High dosages in the vitreous andposterior segment of the eye can beachieved by transseptal (located directlyoutside the eye ball) corticosteroidinjections. Short-term preparations(dexamethasone) or long term prepa-rations (triamcinolone acetonide) areavailable. In the presence of a highdegree of inflammation, chronic cystoidmacular edema (CME) or choroidal neo-

vascularization (CNV), corticosteroids(triamcinolone acetonide) may also beinjected into the vitreous or anteriorchamber. Due to poor compliance inchildren, injection may require a generalanesthesia. No data are provided yetabout the use of the recently introducedintravitreal inserts with corticosteroiddepots (fluocinolone) in the treatmentof uveitis in childhood.

High corticosteroid dosages in both theanterior and posterior eye segment canalso be gained by systemic treatment.This can be achieved by the oral route,or by intramuscular or intravenousinjection, the latter is named “bolus”therapy.

For anterior uveitis, steroids are com-monly applied topically. For inter-mediate or posterior uveitis, steroids arepreferentially given as injections orsystemically. During the chronic courseof disease, combined topical andsystemic steroids, eventually combinedwith immunosuppressive drugs maybe necessary.

Corticosteroid Use:Benefit versus Side EffectsIn many children, quiescence ofinflammation can be achieved withcorticosteroids in more or less highdosages. While long-term remission isintended with continued dosages, there


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is a considerable risk of untoward sideeffects. The critical threshold betweenbenefit and side effect is not welldefined.

As in adults, the major side effects fromtopical application are cataract for-mation and glaucoma. The rate ofcataract induction increases in a dosedependent manner. The typical systemicside effect is Cushing disease. Cha-racteristic symptoms vary, but includeobesity, rounded face, slowed growthrates, thinning and stretch marks ofthe skin, weakened bones, fatigue, weakmuscles, high blood pressure, highblood sugar, irritability, anxiety, de-pression, excess hair growth andirregular menstrual periods. Frequentapplication of eye drops or repeatedtransseptal injections may also lead tosystemic side effects. The criticalcorticosteroid dosage that may be safeis not well defined. The higher anti-inflammatory potency and dosage arethe more side effects can be found.For the long-term use, eye drops shouldbe given ≤ 3 times daily and oralprednisone should be used at dosagesless than 0.1mg / kg bodyweight daily.

In patients with ocular hypertension,rimexolone 1% may be preferred as eyedrops, as it has a lower risk to raise theintraocular pressure. Fluorometholoneformulations may be preferred as along-term maintenance treatment in

patients with low-grade anterior uveitis,as it has a lower risk for cataractformation. As dexamethasone is a phos-phate-buffered solution, it may not beused in patients with high risk fordevelopment of band-keratopathy, e.g.in anterior uveitis in JIA patients.

Recurrent acute AnteriorUveitisTreatment should be instituted as soonas possible after the patient experiencesthe typical signs for acute uveitis.Corticosteroids are started at highdosages, e.g. every 30 to 60 minutes,and are tapered off slowly. Highly potentcorticosteroid formulations are pre-ferred initially (prednisolone acetate 1%,dexamethasone 0.1%). If disease is verysevere, additional regional injections,preferably of short-term corticosteroids(dexamethasone) are given in childrenthat may tolerate the injection. Com-monly, systemic corticosteroids areadded with a tapering within severalweeks. In this type of uveitis, systemicnon-steroidal immunosuppression israrely necessary.

Iridocyclitis in juvenileidiopathic ArthritisUveitis is common in oligoarthritis(inflammation of a few joints Figure 1)and RF(rheumatic factor)- negative poly-arthritis (inflammation of multiplejoints). Up to 25 % of the patientssuffer from chronic anterior uveitis.

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It is important to know that the inflamedeyes generally appear as a white globe(Figure 2). As visual loss is frequent,an aggressive treatment may be re-quired.

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A complete abolition of any cell in theanterior chamber must be obtained. Astep-ladder approach has been sug-gested. In general, treatment is initiatedwith a trial of prednisolone-acetate 1%at high dosages. When inflammation isunder control (means: no cell in theanterior chamber), the topical cortico-steroids are tapered down slowly withinseveral weeks. If complete quiescenceis obtained with 3 drops or less daily, thismay be continued. The dosages aresubsequently reduced to the lowestpossible level, and replacement with aless potent formulation (rimexolone,fluorometholone) may be preferred.Topical non-steroidal anti-inflammatorydrugs alone do not appear to be effectiveto obtain or maintain quiescence of in-flammation. Transseptal corticosteroidinjections may be given in selectedcases (children old enough to tolerateinjection; otherwise under generalanesthesia), e. g. with hypotony ormacular edema.Due to the untoward side effects andlack of efficacy, long-term use ofsystemic corticosteroids is not sug-gested. When long-term quiescencecannot be achieved with low-dosecorticosteroids, immunosuppression isindicated even in the absence of visionthreatening complications or visual loss.

Pars planitis andintermediate UveitisPars planitis (intermediate uveitis

Figure 2: This "white eye" seemswithout inflammation, but it hasmasive cells in the anterior chamber.

Figure 1: Oligoarthritis of the kneein juvenile idiopathic arthritis, oftenassociated with anterior uveitis inchildren.


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without associated systemic disease) isquite common in childhood. It involvesvitreous, ciliary body and peripheralretinal vessels. Deterioration of visionmay arise from vitreous opacity, CME,cataract formation or epiretinal mem-brane formation. Pars planitis may be asevere disease with the risk of visual lossthat needs to be treated aggressively.Corticosteroid eye drops are not helpful.Although regional corticosteroid in-jections (triamcinolone) through thelower lid may be preferred, this maynot be possible in childhood withoutgeneral anesthesia. Therefore, oralcorticosteroids are commonly given.However, immunosuppression (e.g.methotrexate or cyclosporine A) maybe indicated in patients not respon-ding properly or in order to reducethe systemic corticosteroid dosage, toprevent side effects, e.g. cataractformation.

Treatment of uveiticComplications withCorticosteroidsCorticosteroids are of particular im-portance for the treatment of CME (seeuuvveeiittiiss 1-2005). It has been repeatedlyshown that improvement of vision inuveitis patients can be obtained withcorticosteroids. Previous studies havesuggested that transseptal cortico-steroids have a positive influence oninflammatory activity, vision and CME.This has also been demonstrated for

oral, intravenous and deep intra-muscular routes. Several studies haveshown that CME in uveitis patientsmay completely resolve after anintravitreal injection of triamcinoloneacetonide. However, improvement wastransient in many of the patients.

ConclusionAs true in adults, corticosteroids arealso the first line of drugs for uveitis inchildren. Side effects may be profound,such as cataract formation, and difficultto be diagnosed (elevation of intraocularpressure, depression). Recently it hasbeen shown that corticosteroids, andespecially in the therapy for anterioruveitis associated with juvenileidiopathic arthritis, should not be givenexcessively long or at high dosages, thatthey may be substituted by immuno-suppressive drugs quite early.

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Thoughts about SteroidTreatment for UveitisThere is a huge amount of different opinion and information available now aboutsteroids, regarding both their advantages and disadvantages. Often it is difficult forpatients to recognise what is important and what to be aware of when they aresupposed to start steroid treatment. Unfortunately, patients will hear a lot of differentopinions about steroids, depending on who they are talking to. It would make thecooperation between all the involved parties much easier if they understood steroidsbetter. Here, we summarized the response of an Ophthalmologist, an ophthalmicnurse, who has a lot of experience with uveitis patients, and finally of a patient. Wewant to see their different viewpoints, according to the question: ““WWhhaatt aarree tthhee mmoossttiimmppoorrttaanntt tthhiinnggss aabboouutt sstteerrooiiddss??””

From the Standpoint of anOphthalmic Nurse

Zania McKenzie is a nurse with a spe-cific remit to work with uveitis patientsin a uveitis clinic in Edinburgh in theUnited Kingdom.

Professional Relationshipbetween Patient, Nurse andDoctorFor a patient to gain the maximumbenefit from treatment with steroids,it is essential to build a trustingprofessional relationship with thedoctor/nurse. The patient - nurse -doctor “team” should feel comfortableenough to discuss any aspect of con-cern, and treatment compliance,

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because corticosteroid treatment hassuch individual requirements anddiverse considerations regarding qualityof life, including general health, fit-ness, diet and lifestyle.

I really do feel that the dosage, benefits,risks, compliance etc. should beprivately and sensitively, also honestlydiscussed with patients. If the realitiesof steroids are "bluntly" listed in publicprint, then I think more problems couldarise with lack of trust and refusal totake them. Non compliance with steroidtreatment can lead to a serious risk ofpatients permanently losing their sight.


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If patients are taking any medicinesincluding steroids for any reason orcondition (other than uveitis), they mustdiscuss these with their doctor / nurseso that they can make sure that theydo not react adversely with uveitistreatment.

Common Misconceptionswith SteroidsPatient's misconceptions about steroidsneed to be identified regarding in-formed consent to treatment and on-going compliance.

Anabolic steroids have receivedincreased public awareness throughbody building drugs that “mimic” themale hormone Testosterone. These aresometimes prescribed by a doctor ifnatural male development doesn'toccur. Unfortunately they are some-times illegally obtained to enhancecompetitive sports performance andcarry long term health risks. They wouldnever be prescribed for the treatment ofuveitis.

Female gonadotrophic hormonesare steroids that have received increasedpublic awareness through infertilitytreatment for women. They are notprescribed for treatment of uveitis.

From the Standpoint of anOphthalmologist

John Olson is a Consultant OphthalmicPhysician at the Aberdeen Royal In-firmary in Scotland

EfficiencyIt is vital to both doctor and patient thatthe corticosteroids work, not only thatthey work but they should work veryquickly. When sight is affected there isnaturally concern that it has been lostfor good. The rapid recovery that occurswith steroids brings hope, optimism andconfidence to the relationship betweendoctor and patient. This is important asfor a significant few treatment is goingto be prolonged with various challengesalong the way.

Is the Diagnosis correct?If they do not work quickly then thisis a red flag to the doctor indicating thatperhaps this is not inflammation on itsown. Infection is a rare cause ofinflammation in the eye, but can oftenbe cured or at least aided by antibioticsor other anti-infective treatments. In-fection is not always easy to identify astaking a sample of the eye risks affec-ting its very function. This red flag istherefore a very important signal tellingthe doctor to think again.

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How to handle theSteroid-TreatmentSteroids do not come without cost.In the first few days of treatmentpatients often notice an effect on theirmood. Usually they feel more cheerfuland more energetic. The downside isthat they often find it very difficult tosleep at night. If you are prone to a lowmood this occasionally is worsened andvery rarely patients hallucinate. Withinthe first few weeks of taking steroids,particularly if large doses are giventhrough a drip, then patients may no-tice their “teenage acne” returning.Thankfully steroid acne usually sparesthe face and affects the chest. Both theseside effects resolve on reducing thedose. It is important, however, not tomake any important or life-changingdecisions whilst on high dose steroidsas you may not be thinking exactlyas you would do normally.

After the relief of their sight improvingpatients and doctors then start to focusmore on the long-term side effects ofsteroids. One of these problems starts ifyou stop your steroid tablets too quickly.The usual reasons patients give me are“my prescription ran out and I thought Iwould wait to see you again” or “Istopped taking them because they mademe feel miserable”. Steroids are strangebeasts. Usually if a tablet makes you

feel unwell then the advice is to stoptaking it. With steroids you mustnever do this without seeking medicaladvice first. Why is this?

Our own body normally makes theequivalent of about 7.5mg of predni-solone a day. Your own steroids help youkeep your blood pressure at the rightlevel and also help you fight the “stress”infection puts on the body. When youhave an infection your body willnormally make twice as much steroid tocope. If you have too little steroid “onboard” and an infection hits then yourblood pressure drops, you feel awful,you may black out and you may becomeunconscious. As well as this you oftendevelop diarrhoea. In this situation youmust get more steroids on boardimmediately. If you have diarrhoea,steroid tablets will often be ineffectiveas they just pass through and you maywell need an injection. It is difficult tobe precise but your steroid card shouldtell you how much to increase yourmedication by and you must seek ur-gent medical help.

Why doesn’t the Bodyrealise this and just makemore Steroids?If you take steroid tablets, the pituitarygland detects this in the blood, whichfloats past it at the base of the brain. It is


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the “conductor” of the endocrine “or-chestra”. Normally it sends a messageto the adrenal glands on top of yourkidneys telling it how much steroid tomake. The dose of prednisolone youwill have been given to start with is farhigher than the body would produce.The pituitary gland detects this, stopssending any more messages to theadrenal glands and basically goes onholiday. Unfortunately if you stop ta-king steroids too quickly the pituitarydoesn’t bother rushing back from itsholiday. It can take months before itstarts working properly. The bottomline is: do not stop taking your steroidtablets without medical advice.

How to handleSide EffectsA while after starting steroids, oftenwhen the dose of steroids is quite small,patients may start to notice that thereface may be round and that they haveput on fat on their abdomen but nottheir legs. This is the cushingoidappearance that used to mark out manypeople on steroids. As long as theprednisolone is kept in single figuresit will go with time. If the steroid doseis kept high and the weight gain persiststhen there is a risk that diabetes willoccur. Normally a hormone called in-sulin, which is made in the pancreas,tells the body to pick up the food it needsfrom the blood stream. If your bodybecomes “too big” there is not enough

insulin to go round and you leave foodbehind. Also if you have too much fatyour own insulin seems to work lesswell. This leads to high sugar levels,which damage your blood vesselsmaking you at risk of heart attacks,strokes, kidney disease and problemswith eyesight, if it is not managedproperly. As the mainstay of treatmentfor diabetes is controlling what youeat, this can be quite difficult.

Steroids also cause the body toretain salt. This increased salt level,particularly in the blood, drags waterwith it raising the pressure within theblood vessels. This can cause your an-kles to swell and cause hypertension,another cause of damaged bloodvessels. This can easily be managedwith tablets but the best approach isto reduce the dose of steroids.

Steroid tablets can also cause weakeningof the bones (osteoporosis). This iscompletely painless unless the bonecrumbles or breaks. The bones mostcommonly affected are the back and thehip. If the bones in the back are brokenthis can cause a lot of pain. The patientwill lose height and if more than onebone is affected the patient can becomestooped with the head falling forward.This is much like the figures seen onroad signs to indicate the presence ofelderly people. Taking preventativemedication once a week, walking

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regularly, avoiding cigarettes and notdrinking too much alcohol can largelyprevent all this. As it is related to thetotal amount of steroid you haveconsumed, amongst other things, it isanother reason why doctors are keen touse other treatments as well as steroids.

Why do we use Steroidsif they are so dangerous inthe long Run?Steroids work very quickly andmost of our other treatments take along time to work. It is a bit like shutt-ing an overfull suitcase. The steroidsare the big weight to enable you toclose the lid. Once the lid is closedthen the latches can be used to keepit shut. Trying to shut the lid by pull-ing the latches together is largelyineffective. So what do we do? We usesteroids to get control and if you needmore than a small amount to keep theinflammation away we encourage youto use other drugs as well. It is betterto use small amounts of a few drugsthan large amounts of only one drug,as the risk of side effects is usuallyfar less.

ConclusionAll this sounds a bit doom and gloom.However, this is why we need specialistdoctors trained in uveitis. Withexperience and careful use of drugs,these uveitis specialists will enable manypatients to retain their sight, free fromsignificant side effects.

From the Standpoint of anUveitis Patient from the UK

CR: a patient with posterior uveitis

About the Fear ofSide EffectsAs a healthy person who had discoveredin the ‘prime of life’ I had an eyecondition which was going to needtreatment with steroid drugs, the firstthing I remember was having a naturalaversion to taking drugs in general. It issomething some of us seem to beconditioned with, even being reluctantto take paracetamol for a headache.

Steroids seemed to be such a familiarterm and it is impossible to think ofsteroids without thinking of visions ofbanned athletes, although it doesn’ttake long to realise that corticosteroidsare completely different. The next thingto come to mind about steroids is thatthey just don’t sound like a goodthing, - they seem to have a badreputation. Don’t they have side effects,putting on lots of weight, or getting afunny shaped face?At first, you realise you have viewsabout taking steroids long before youhave considered any proper factsabout them. The next step was tofind out about them. The internetdefinitely comes to mind when lookingfor medical information but “Google”comes up with millions of results for


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steroids (nearly 19 million actually).Next there are patient informationleaflets that come with the drugs andthese list an extraordinary number ofside effects, most of which seem toappear on every type of drug infor-mation you read.The thing I couldn’t work out is whetherI was going to suffer all, some or noneof these side effects. What were thechances of suffering the side effects,compared to catching a cold or beingrun over by a bus?I eventually decided that I couldn’treally decide just how bad or not theside effects would be and so I felt Ineeded to speak to someone to get arealistic idea of what to expect.I think this is where being able tospeak to someone at the clinic or beingable to speak to someone from a patientsupport group is the best way to knowwhat to expect.

In the end the side effects that mostaffected me were the ‘psychological’ones. Changes in mood and feelingtired unpredictably were harder to dealwith than the physical side effects whichI found didn’t really affect me much.

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Patient

Steroids in Uveitis:Patient Reports

Patient Report fromGermany

Before 1996 until the treatment withSteroids there was a permanent wor-sening of my visual acuity which wasdue to a rare form of posterior uveitis,the so called Birdshot Chorioretinopathy.By estimation, this is seen in Germanyin less than 100 persons. Because ofinflammation of retinal vessels, botheyes developed vitreous inflammationand massive oedema of the macula.The regular ability to read soon wasgone: Night blindness, vision through atunnel, looking like through a fog,and reduced vision of colours werecharacteristic for my vision.

Because my disorder is a posterioruveitis only steroid tablets seem tobe effective, because topical steroidswill not reach the retina in adequatedosage. Normally one starts thetreatment with high dosages at thebeginning. After this, the dosage willbe reduced in multiple steps until thesteroids were stopped.

My first treatment course started with75 mg of prednisolone per day andinduced a nearly prompt improvementof my disease. After five steps ofreduction I had reached 20 mg ofsteroids and this was when worseningoccurred. After three months with 5 mgthis treatment was stopped and a se-cond course was started with 50 mg ofsteroids, which finally ended with2.5 mg. Again we found steroids veryeffective for my disorder, but only inhigh and medium dosages.

In both courses I had observed thaton the one hand the side effects weremore when the dosage was high, onthe other hand my body was veryirritated when I had reached the lowdosages. In times with high dosages Ihad sleeping problems, reduced weight,had an euphoric affect, “doping-like”increase of my power, muscular crampsand diarrhoea. In case of heavy re-duction of the steroids, I realised ex-haustion, listlessness, sleeping pro-blems, melancholy and problems withmy circulation. But I never realizedother often described symptoms like


weight gain, a moonface or elevationof blood pressure, although I havetaken steroids for nearly 4 years.Evidently there is an individual com-ponent playing a major role for theseside effects.

I had noted that the rate of reductionof steroids affected some changes ofthe reaction of my body. In the hopeto find a relation between a highpercentage reduction of steroids andthe problems of my body, I countedthe percentage of changes for eachstep of steroid reduction. In some stepsI really was able to see such aconnection. Of course, using a fewobservations, this connection is not aproof from a statistical side. Despitethat I did not have any other ideas, soI started from the working hypothesisthat from a certain percentage of steroidreduction the body becomes irritatedand the danger of a uveitis recurrencemay exist. For all steps of reduction, Ihave chosen the same percentage valueand fixed that relatively low on 15percent, to reduce the risk of a re-currence as low as possible.

This third course of steroid treatmenthad been started with 60 mg per day.With the slow reduction rate of 15percent, multiple steps were neededuntil the steroids were stopped. Onaverage after 5 days the dosage wasreduced until 10 mg, to limit the whole

time of steroid treatment even more.After this I choose time periods ofthree to four weeks.To reduce the danger of unrealizedworsening of the macular edema, Iused the well-known Amsler Grid.Additionally I established my dailyreading test: I prepared the sentence“This is a test” in different large letterson one sheet of paper and I used toread this sentence separately with botheyes having the goal in mind, that withreduced visual acuity I would not re-duce the steroid dosage anymore. Lateron I also transferred such a readingtest into the distance: I prepared aposter and tried to read the letters invarious meters of distance.

For counting the results of this steroidcourse correctly I also have to mentionthat in addition to steroids I partly hadtaken mycophenolate mofetil, cyclo-sporin A and interferon, drugs whichdefinitely may have covered the reac-tion of steroids. But I can report, thatfollowing my observation the extremestrong reaction, which was found inthe first and second course of massivesteroid reduction, was not seen in thisthird course using 15 percent reductionrate of steroids. Until reaching a dosageof 2.5 mg of steroids – without treatmentof interferon – there was no recurrence.The uveitis was burned out; but Irealized a therapy resistant macularoedema, which finally resolved after afew days with interferon treatment.

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Patient

How long will it take until a reducedvisual acuity (after a recurrence)responds to higher steroid dosages? Inmy case the steroid dosage was elevatedfrom 2.5 to 15 mg after such a re-currence. With my visual test, men-tioned above, I realized that my badeye needed 25 days and my good eye15 days to reach my old visual acuity.

Jürgen Freytag

Patient Report from Italy

Since 2004, uveitis entered my lifeand nothing has been the same. Pre-viously I had never known even thename. I thought that maybe the stresswas the trigger for this disease, and Iwas scared about the possible sideeffects of the suggested steroid treat-ment. My red eyes, so sensitive tolight, my blurred vision, were terribleelements that have changed my life.

The first doctor I met, said that the bestapproach would be dexamethasone eyedrops 6 times a day for one week andthen decrease the dose gradually; ap-parently it worked: my eyes becamewhite and the pain disappeared. Oneweek after the end of the treatment therewas a violent relapse. The doctor thatgave me the first care said that thetreatment I had done was effective andsuggested to repeat it, but this time it

was not effective: I decided to callanother doctor.I was admitted to the hospital, examin-ed for several blood tests, x-rays, andmany more procedures. Fortunately,nothing was wrong. At the same timeI received 3 injections “near” my righteye (he called them “sub-tenon in-jections”) and I recovered my sight,without any side effects, continuing toput steroids eye drops in both eyes. Isupposed to have reached the end ofmy nightmare.I was not right.

So, another doctor tried to help merepeating the same treatment: anotherdoctor, same therapy, same failed re-sult. Nothing changed and somebodysaid that in another center in Italy Iwould find the answer for my personaltragedy.

The “new” doctor said that I had ancondition called “Behçet´s Disease”,telling that the anterior uveitis wasnot so aggressive and the best optionwould be…topical eye drops! It is easyto understand that the result was notso impressive.

Another relapse, another travel, anotherdoctor, same therapy. But that time,the last doctor, who thought that thediagnosis I had received was not right,referred me to a “tertiary referralcenter”, where I have met a doctor, my


even taking acetazolamide orally, theraised pressure was not under control.The doctor decided to remove the steroidin my scleral tissue, thinking about thepossibility to do also a surgical pro-cedure called “trabeculectomy” if thatoperation would be not effective. But itwas: 2 weeks after removing my steroiddepot, my pressure was completelynormal.

Now, I’m on a low dose of systemicsteroids, my eyes’ pressure is normal,my sight is quite good, and I’m fine:for the first time I’m feeling “normal”.I have got an opinion: steroids haveseveral possible side effects, but if youknow them, you should not fear them;so, you don’t need only steroids, youneed a doctor able to look into youreyes like a friend, able to give thestrength to fight, a sort of “specialguide”: the last doctor, my doctor,did it.

Pietro Baldassarre

doctor, probably the only one thatreally knows about uveitis.

My sight was particularly affected inthe left eye because of a complica-tion called “cystoid macular edema”,possibly generated by the long action ofthe ocular inflammation. He said: “It isnecessary to change the strategy: youhave never used systemic steroids andthey are necessary to stop the long-standing inflammation, but you haveto carry the temporary side effects. Thiswill be not simple, but you haveto fight and win. Oral prednisoneshould help you.”

The summary of that strategy was:no more topical, but systemic steroids.I had no severe problems with tem-porary side effects due to systemicsteroids, and after 2 months my sightrecovered almost completely, but asmall amount of cystoid macularedema persisted and we decided tohave a sub-tenon injection of tramcino-lone (another different steroid) tocontrol the inflammation better. Mysight totally recovered, but another“enemy” was ready to fight against meand my eyes: raised intraocularpressure.I felt fear.

The fight was long and hard: for a longtime I put in my eyes anti-glaucomadrops to control the high pressure, but

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uveitis

Physicians and Uveitis

thought were the best 4 articles. Thisresulted in a list of 13 clinical and 12experimental articles. In the final roundeach expert had to give points to four ofthese nominated papers (5, 10, 20 and30). In July (for the experimentalawards) and in August (for the clinicalawards) the winners were notified.Because no other uveitis awards exist,the winners were very happy.

What was the Content ofthe winning Articles?Until today the mechanisms leading touveitis are not well known. Most of theexperimental work today is currentlyundertaken in animal experiments.There are models of uveitis in mice

How the Winners wereselectedAs in the previous year there were twoaward categories, one in the field ofexperimental and one in clinical uveitisresearch. A team of 6 experts had tochoose the best 3 publications in eachfield, published in the scientificliterature of the year 2004. “ScientificLiterature” relates to journals wherearticles undergo peer review (meanslikely to be important and new). Thissecures a high grade of quality in itself.The money award goes to the firstauthor, the document of honour tothe whole group.In the first round, each expert had beenasked to nominate what he or she

News from the Scientific WorldThe Uveitis Awards from the German Uveitis PatientsInterest Group (DUAG) 2005

Since 2003 the DUAG has supported uveitis research by donating awards to clinicaland experimental uveitis research. One of the main goals within the constitution ofthe DUAG is to achieve “support of scientific research”. In September 2005 theawards were presented during the congress of the SOE (European OphthalmologySociety) in Berlin, Germany. In the experimental field there were two first awards, andin the clinical field two second awards. Here, the winners presented their awardwinning articles to the congress audience. Our readers will find a summary on thefollowing pages. Prof. Manfred Zierhut, the President of the DUAG, describes theprocess to select the winners and the topics of the winning papers. As in previous years,Bausch & Lomb Co., Rochester, USA, sponsored the awards. We would like to thankthis company very much for their support!


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and rats which are very importantsince they very closely mimic the humanuveitis. The first article (Smith and co-workers) investigates a major cause ofposterior uveitis, induced by the parasiteToxoplasma gondii, and why thispreferentially induces retinal disease.The second article (Xu and co-workers)reports about experiments which aredesigned to find out how inflammatorycells find the eye as their destination,leading to uveitis. The third article (deKozak and co-workers) reports onimprovement of treatment by using verysmall particles, called nanoparticles.

The clinical articles reported on twowell known uveitis types, the final oneabout investigations to analyse the roleof white blood cells and why they areso active in uveitis inflammation. Thefirst report (Rothova and co-workers)dealt with the prognosis of the so-calledBirdshot-uveitis, a posterior uveitiswhich is characterized by a typicalclinical pattern. The second paper(Tugal-Tutkun and co-workers) studieda huge population of Turkish patientswith the so-called Behçet´s uveitis, amultiorgan disorder. The third article(Curnow and co-workers) investigateslymphocytes (white blood cells) andtheir role in the anterior chamberduring a uveitis.

Why do we need UveitisAwards?The DUAG awards are still the onlyuveitis awards. This is even morespecial because they are donated in thename of an ocular disease patientinterest group. We plan to establish theawards as a qualification criterion inthe coming years so as to help thewinners in their careers giving them abetter chance of obtaining researchgrants and thereby expanding researchinto uveitis.As in previous years, the AwardCommittee and the DUAG agreed thatall six awarded publications offer animportant new aspect in themanagement of clinical uveitis orimprove our knowledge regarding themechanisms playing key roles inexperimental uveitis, therefore proba-bly delivering ideas for new therapeu-tic targets. Making new scientificresults more easily and quickly avail-able to ophthalmologists, and also tohealth insurances, is a major goal forpatient interest groups in all countries.This will ensure a modern and moresuccessful approach to diagnosis andtherapy for uveitis-patients.


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1st award Smith JR, Franc DT, Carter NS, Zamora D, Planck SR,

Rosenbaum JT.

Susceptibility of retinal vascular endothelium to infection withToxoplasma gondii tachyzoites.Published in: Investigative Ophthalmology & Visual Science 2004; 45 : 1157-1161.

This paper describes our investigation of the interaction between Toxoplasmagondii (T. gondii) and endothelial cells (cells that line the blood vessels) of theretina. Toxoplasmic retinochoroiditis, the commonest form of retinal infectionworldwide, has been the subject of the edition of uveitis (2/2005). The T. gondiiparasite may be contracted by eating undercooked meat or by ingesting materialthat is contaminated with cat feces. It may also be passed from an infectedpregnant mother to her unborn child. After entering the body, the parasiteprefers to lodge in the retina and brain than other organs. The reason for thispreferential localization is unknown. One possibility is that the eye and brain donot fight infection as vigorously as elsewhere in the body. Another possibility isthat the parasite penetrates these tissues more easily than other organs. To enterthe retina, T. gondii must cross the retinal endothelial cells (the inner cell layerof retinal vessels). We hypothesized that retinal endothelium was moresusceptible to infection with T. gondii than other endothelium.

To test our hypothesis we measured the susceptibility of different endothelialcells to T. gondii infection using a method called the [3H]-uracil incorporationtest. In these experiments, cells from a human being are grown in a dish. Whencells completely fill the dish, they are infected with T. gondii. A chemical calleduracil - that is joined to a radioactive label, [3H] - is added to the dish; T. gondiiparasites need uracil as they grow inside the cells. One day later the amount ofradioactivity ([3H]-uracil) in the dish is measured. The measurement indicateshow well T. gondii grew inside the cells in the dish. If the radioactivity is high (ie,T. gondii encorporated lots of [3H]-uracil), T. gondii grows well in the cells. Inother words, if the radioactivity is high, the cells are very susceptible to infectionwith T. gondii parasites.

The experimental Uveitis -Awards


We compared retinal endothelium with endothelium from other parts of thebody, including the aorta (which is the large vessel that runs through the chestand abdomen), the placenta and the skin. We observed that retinal endotheliumyielded the highest radioactivity readings of all cell types tested. From this workwe were able to conclude that cells lining the blood vessels of the retina weremore susceptible to T. gondii infection than cells of blood vessels elsewhere inthe body. This may explain, at least in part, why T. gondii infects the eye ratherthan other body organs. Presently we are focusing our research on under-standing what causes this susceptibility to infection. It may relate to: strongattachment between T. gondii and the retinal endothelial cell; fast division ofT. gondii within the endothelium; and/or chemicals produced by the infectedcells that help T. gondii to grow.

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Fig.: 1 st experimental Award – from the left tothe right side: Justine Smith (Portland),Matthias Becker (Heidelberg / DUAG)


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1st award Xu H, Manivannan A, Jiang HR, Liversidge J, Sharp PF,Forrester JV, Crane IJ.

Recruitment of IFN-gamma-producing (Th1-like) cells into the inflamedretina in vivo is preferentially regulated by P-selectin glycoprotein ligand1: P/E-selectin interactions.Published in: Journal of Immunology 2004; 172: 3215-3224.

The main concern for uveitis patients is to get the inflammation under controlpromptly and effectively. Although treatment of uveitis has improved over thelast decades, current therapies are non-specific and associated with major sideeffects. Alternative therapies with more specific anti-inflammatory effects andfewer side effects are therefore urgently needed. During inflammation,inflammatory lymphocytes (white blood cells) are constantly recruited from theblood vessels into the inflamed tissue. Preventing the recruitment ofinflammatory cells should therefore effectively control inflammation.

The first step of inflammation of the eye starts, when lymphocytes, the so-called adhesion molecules and structures of the eye like retinal blood vesselsinteract. Adhesion molecules are proteins, which interact between lymphocytesand the vessel, resulting in an uptake of the inflammatory cell into the eye.Always two adhesion molecules (one on the lymphocyte, one on the vessel)interact. Our study aimed to understand the mechanism that controls migrationof inflammatory cells from retinal blood vessels into inflammatory retinal tissue.Experiments were carried out in mice with experimental autoimmuneuveoretinitis (EAU), an animal model for human uveitis. CD4+ T cells, onesubset of the white blood cells, are believed to play important roles in thedevelopment of uveitis. Three types of CD4 T cells namely naïve CD4 T cells;IFN-gamma-producing (Th1-like) CD4 T cells and non- IFN-gamma-produ-cing (Th2-like) CD4 T cells were labeled with fluorescent dye and thentransferred into mice with uveitis (EAU). Movement of the labeled cells in theinflamed retina was recorded digitally using a cell tracker system calledscanning laser ophthalmoscope (SLO). We found that more Th1-like CD4 T cellsrolled in the inflamed retinal vessels and later migrated into inflamed retinaltissue as compared to naïve CD4 T cells and Th2-like CD4 T cells. Furthermechanism study revealed that adhesion molecules such as P-selectinglycoprotein ligand 1 (PSGL-1) and LFA-1 were expressed at higher levels on


Th1-like cells, whereas another adhesion molecule, CD44 expressed hig-her on Th2-like cells. In the inflamed retina P-selectin, E-selectin, and ICAM-1were up-regulated on the vessel segments with inflammation. Th1-like cellswere not able to infiltrate the eye, when the interaction of PSGL1 on Th1-likeCD4 T cells and P/E-selectin on inflamed retinal vessels with an antibodyagainst PSGL1 was blocked. On the other side, anti-LFA-1 antibody whichblocks LFA1 on inflammatory cells, and ICAM-1 on retinal vessels and anti-CD44 antibody which blocks CD44 on T cells and hyaluoronic acid on retinalvessels inhibited the infiltration of both Th1- and Th2-like cells.

Our data suggest that random movement of activated CD4 T cells (both Th1-and Th2-like CD4 T cells) across the retinal blood vessels is mediated by theadhesion molecule pair CD44:CD44 receptor and LFA-1:ICAM-1 interactions.Preferential recruitment of Th1-like cells, especially important for the initia-tion of uveitis, is mediated by PSGL-1:P/E-selectin interaction. Treatmentdesigned to block the interaction between inflammatory cells and blood vesselwall such as PSGL1:P/E-selectin interaction in uveitis could prevent inflam-matory cell infiltration and therefore effectively control the inflammation.

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Fig.: 1 st experimental Award – from the left to the right side:Hans-Jürgen Werndt (Bausch & Lomb), Heping Xu (Aberdeen, UK),Silke Greif (Essen / DUAG), Manfred Zierhut (Tübingen, / DUAG)


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3rd award de Kozak Y, Andrieux K, Villarroya H, Klein C, Thillaye-Goldenberg B, Naud M-C, Garcia E, Couvreur P.

Intraocular injection of tamoxifen-loaded nanoparticles: a new treatmentof experimental autoimmune uveoretinitis.Published in: European Journal of Immunology 2004; 34: 3702-3712.

Experimental autoimmune uveoretinitis (EAU) is a well-established model forstudying uveitis in humans. It is a CD4+ T lymphocyte-mediated disease inwhich macrophages play an important role as effector cells of the intraocularinflammation. To induce EAU, laboratory animals are immunized with retinalautoantigens, such as S-Antigens. This experimental model has been used toevaluate the effect of drugs, which now are successfully used in humans. Someof these agents are used currently in clinical practice (e.g. corticosteroids,cyclosporine), however, these therapies are frequently complicated by systemicside effects. In such a S-Ag-induced EAU in rats, we tested the efficiency of anintravitreal injection of tamoxifen, a non-steroidal estrogen receptor modulator.To avoid side effects observed when tamoxifen is used in high doses and/or forlong periods of time, we encapsulated tamoxifen into nanoparticles beforeadministration to rats with EAU. We first investigated the localization of thenanoparticles within the eye using fluorescent labeled PEG-coated nanoparticlesafter injection into the vitreous cavity of rats with EAU. Whereas the injection offree tamoxifen did not alter the course of EAU, intravitreal injection oftamoxifen loaded into nanoparticles resulted in significant diminished ocularinfiltration by inflammatory cells. So, the interaction of tamoxifen with estrogenreceptors in macrophages could have altered the antigen presentation. Inaddition, there was a switch to regulatory Th2 type of response which is moreprotective for the eye. Our results suggest that tamoxifen, released continuouslyfrom ocular cells, could reach the immune system through the blood, thusreducing the uveitis activity.

In conclusion, the use of intravitreal administration of tamoxifen loaded ontonanoparticles allowed us to decrease the amount of the drug delivered: 250ng/eye compared to 200-800 ng/mice in other experimental disorders. Thisshould reduce possible ocular side effects as observed after systemicadministration of high doses of tamoxifen. Although new drugs with uniquetherapeutic properties may be discovered and synthesized, their administration

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for the purpose of treating ocular inflammation remains a major challenge. Theencapsulation of biologically active molecules may increase their bioavailabilityand may induce a sustained release, thus avoiding repeated intraocularinjections.

Fig.: 3 rd experimental Award – from the left to the right side:Manfred Zierhut (Tübingen / DUAG), Yvonne de Kozak (Paris),Hans-Jürgen Werndt (Bausch & Lomb)


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1st award Rothova A, Berendschot TT, Probst K, van Kooij B, Baarsma GS.

Birdshot chorioretinopathy: long-term manifestations and visual prognosisPublished in: Ophthalmology 2004; 111: 954-959.

In this research project, two uveitis research groups from large centers collabo-rated in order to examine long term prognosis of a puzzling ocular disorder cal-led birdshot chorioretinopathy (BCR).

BCR is an intriguing ocular disease of unknown origin, associated with a speci-al genetic characteristic human leukocyte antigen (HLA), the HLA-A29. BCRusually causes chronic inflammation in both eyes of middle aged persons andmight lead to severe loss of central visual acuity as well as to restricted visualfields. Previous studies on BCR were of short term duration and reported thatdespite the chronicity of the disease, the prognosis was mostly favorable.Therefore, the treatment with immunosuppressants was recommended onlyduring the process of losing visual acuity. However no information was availa-ble on the effectiveness of these drugs, long-term visual prognosis and on thenatural course of the disease.

In our study we examined the clinical characteristics and outcomes of patientsand attempted to evaluate the usefulness of standard treatments. Also we wan-ted to identify characteristics of BCR patients with a high risk for losing visualacuity. Our study included 55 patients with HLA-A29-positive BCR, of whom 37were followed for at least 5 years.

The main findings of the study were the following:1. Loss of visual acuity in BCR was slow and gradual: the number of eyes withlegal blindness increased from 8% at onset of BCR to 30% after 5 years andfinally to 39% after 10 years of follow-up.2. The cause of decreased visual acuity consisted mainly of edema in the macu-la and macular scars. Visual field defects were present in all examined patients,and were unexpectedly large in almost a half of the patients. Abnormal retinalvessels were also observed in the majority of patients.3. Annual loss of visual acuity did not differ between untreated patients andpatients treated by standard therapeutic forms.

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4. In patients with macular edema the long term visual acuity was significantlylower than in patients without macular edema.5. More than half of the patients with BCR suffered also from cardiovasculardisease, mainly from high blood pressure. The patients with BCR and highblood pressure had lower visual outcome than BCR patients without high bloodpressure.

The main conclusion of our study was that the visual prognosis of BCR was poorcompared to patients with other types of uveitis and that the recommended the-rapeutic regimens have not reduced the risk for an annual loss of vision. If wewant a better prognosis for patients with BCR, then we need further studies onthe cause of this disease, so that a causal therapy can be developed. One of thestrengths of this study was the long time during which the patients were follo-wed and the partnership of 2 centers. The teamwork between various centers isvery important while studying unusual diseases like BCR.

Fig.: 1st clinical Award – from the left to the right side:Hans-Jürgen Werndt (Bausch & Lomb), Aniki Rothova (Utrecht,The Netherlands), Manfred Zierhut (Tübingen / DUAG)


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The clinical Uveitis-AwardsPhysicians and Uveitis

2nd award Curnow SJ, Scheel-Toellner D, Jenkinson W, Raza K,Durani OM, Faint JM, Rauz S, Wloka K, Pilling D,Rose-John S, Buckley CD, Murray PI, Salmon M.

Inhibition of T cell apoptosis in the aqueous humor of patients with uvei-tis by IL-6/soluble IL-6 receptor trans-signaling.Published in: Journal of Immunology 2004; 173: 5290-7.

The immune system has evolved to protect the individual from a large range ofinfectious organisms. Although immunity is highly efficient, there can be somedamage to surrounding tissues, even if they were not infected. For the majorityof tissues this bystander damage does not present a problem, as the tissue canvery easily repair itself. However, for a number of tissues any significant immu-ne mediated damage could threaten the viability of the individual. For these tis-sues the immune response is carefully controlled and the tissues are describedas having “Immune privilege”. The eye is a well studied example of a tissue withimmune privilege. This means that any immune response occurring in the eyeshould be very limited, and only result in a minimal level of damage to the tis-sues. It is clear that uveitis contradicts the immune privileged status of the eye,with some patients suffering severe sight-threatening inflammation. Our rese-arch group is attempting to identify the pathways that are altered during theimmune response in uveitis.

One key feature of inflammation in any tissue, including the eye, is the accu-mulation of cells of the immune system, especially lymphocytes. Under normalconditions lymphocytes entering the eye should not persist, instead they shouldundergo a type of cell death termed “apoptosis”. We examined lymphocytes iso-lated from the aqueous humour of uveitis patients but could find no evidencefor these cells entering apoptosis. This suggested that the cells were either una-ble to enter apoptosis properly, or were actively prevented from doing so. Whenwe cultured lymphocytes with aqueous humour fluid from uveitis patients wefound that apoptosis was inhibited. Importantly this did not occur for samplesfrom non-inflamed control individuals. This indicated that the inflamed envi-ronment of the uveitis eye was actively preventing lymphocyte death. The factorsresponsible for this effect were identified as the cytokine IL-6 along with thesoluble IL-6 receptor, both previously known to be elevated in uveitis. Ourresults show that in uveitis, lymphocytes that should normally die by apoptosisare protected by the inflammatory environment, leading to their accumulation.This now provides a potential new therapeutic target for uveitis.


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Fig.: 2nd clinical Award – from the left to the right side:Arnd Heiligenhaus (Münster / DUAG), Ilknur Tugal-Tutkun (Istanbul,Turkey) Manfred Zierhut (Tübingen/DUAG),

Fig.: 2nd clinical Award – from the left to the right side:Philip I.Murray (Birmingham, UK), Manfred Zierhut (Tübingen/DUAG),S. John Curnow (Birmingham, UK), Silke Greif (Essen / DUAG)


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2nd award Tugal-Tutkun I, Onal S, Altan-Yaycioglu R,Huseyin-Altunbas H, Urgancioglu M.

Uveitis in Behçet patients: an analysis of 880 patients.Published in: American Journal of Ophthalmology 2004; 138: 373-380.

The prevalence of Behçet disease is higher in Turkey than in any other country.One third of uveitis cases seen in referral centers in Turkey are diagnosed withBehçet uveitis. In this study we retrospectively analyzed the demographic andclinical features and visual prognosis in our Behçet patients who presented withuveitis between 1980 and 1998. We included 880 patients (1567 eyes).

The disease was more common in males with a male:female ratio of 2:1. The ageat onset of uveitis was around the end of the third decade of life. Male patientswere significantly younger at onset and presented significantly earlier thanfemales and with more severe disease. Ocular involvement was bilateral in 78%of the patients. Panuveitis was the most common type of involvement. Retinalvasculitis and vitritis were the most common findings of uveitis (89%) followedby retinitis (52%). A hypopyon was observed in only 12% of the eyes. The mostcommon complication was macular edema (45%) followed by cataract (39%). Anoptic atrophy was observed in 24% of the eyes. Visual acuity at initial visit was0.1 or less in 41% of the eyes. However, since visual acuity may be severely affec-ted during inflammatory episodes and may improve when the inflammationresolves, we defined potential visual acuity as the best visual acuity recordedduring the first remission period at the beginning of follow-up. Potential visualacuity was 0.1 or less in 31% of the eyes in males and 24% of the eyes in fema-les. Thus male patients had more severe disease from the onset of uveitis. Wefound that 15.6% of the eyes with a potential visual acuity better than 0.1 lostuseful vision irreversibly during follow-up. We estimated the risk of loss of use-ful vision to be 6% at 1 year, 17% at 5 years, 25% at 10 years, and 29% at 20 years.The risk of losing vision was significantly higher in males than in females.However, male patients who presented after 1990 had a significantly lower riskof losing vision than male patients who presented before 1990. Although therewas a similar trend in females as well, a significant difference was not found,probably because the natural disease course is milder in females. Only conven-tional immunosuppressive agents were used during the study period. However,there were changes in our therapeutic approach. In the 1980s we first treated


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the patients with corticosteroids and administered immunosuppressive agentswhen long-term high-dose corticosteroids were required. Cyclophosphamidewas the initial drug of choice during that period. In the 1990s we tried to avoidcorticosteroid monotherapy in patients with posterior segment involvement andadministered immunosuppressive agents early in the follow-up. The initial drugof choice was azathioprine. Cyclosporine was available only during the secondhalf of the study period. Therefore, we speculated that our more aggressive the-rapeutic approach in the 1990s and availability of cyclosporine had improved thevisual prognosis in our patients. We believe that visual prognosis may furtherimprove with the use of new immunomodulators and biologic agents. A studycomparing patients who presented in the 2000s with those who presented inthe 1990s is currently underway at our department.


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Cultural Corner

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I am sure that Ophthalmologists andpatients would agree that one of themajor concerns with uveitis is its placein the field of Ophthalmology. This‘medical’ condition seems to sit uncom-fortably in the mainly ‘surgical’ world ofOphthalmology. This appears to result,in many instances, in a lack of a goodroute for the patient with uveitis; frompatient presenting at their general prac-titioner through to referral to a suitablespecialist to manage the condition.

It was with this in mind that I thought itwould be interesting to see how uveitiswas managed many years ago.To get some idea, we can go back to atext published in 1910, “The ModernPhysician”, edited by Dr. AndrewWilson, the rather severe lookinggentleman pictured besides to give aflavour of the times.

This publication, although considered a‘medical text book’ was also probably aforerunner to the ‘popular science’books of today. It consists of five volu-mes and has some highly entertaining,politically incorrect and / or gruesomereading. A look at the eye conditionschapter proved very interesting.

There is a section titled ‘Iritis’. There isno mention in the book of posterioruveitis as such but sympathetic ophthal-mia is covered as a separate section.Interestingly, the ‘Iritis’ section tookprominence over two much smallersections, ‘Cataract’ and ‘Glaucoma’.Another prominent section here was theserious matter of burns with slakedlime, a reminder of how widespread thelime industry was at this time.

Uveitis – A Look back into 1910Uveitis is not a new disease, its clinical course has been known for a long time.Phil Hibbert, who runs the UIG, the patient uveitis group in the UK, has foundinteresting information about the role, uveitis played app. 100 years ago.

Dr. Andrew Wilson


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Cultural Cornerin shape. If shaded from the light itdoes not dilate or expand so easily asthat of the unaffected eye.”

The section of the old text book on treat-ment shown below demonstrates howfar treatment has come since the early1900’s. We can see from the sectionbelow that the treatment options arepretty limited and apparently a bit ex-treme in some cases.

“The Treatment of Iritis must be under-taken promptly to be successful, and itwill consist of the application of atropinedropped into the eye two or three timesa day. Dry or moist heat may be fre-quently applied in the form of compres-ses (not poultices), and if the pain issevere or the pupil not dilating well, oneor two leeches applied to the temple ofthe affected side may give wondrousrelief.”

However it is worth noting the referenceto hot compresses, a method which pos-sibly is undervalued today, and a methodcertainly encouraged by some uveitisspecialists and specialist uveitis nurses.One UK uveitis specialist has becomeinvolved in the manufacture of micro-wavable compresses, (‘The Eyebag’).I’m not aware of any specialists advoca-ting the use of leeches but I suppose weshould keep an open mind.

References:"The Modern Physician“ edited by DrAndrew Wilson and published in 1911.

Looking closer at the ‘Iritis’ section it isstriking to see what importance wasgiven to this condition.

“It is a most serious ailment, and onethat demands prompt and efficient treat-ment. It is only mentioned here toemphasise its importance, and no oneunskilled in the treatment of eye affec-tions should undertake such a case ifspecial treatment can be obtained.”

It seems that anterior uveitis was consi-dered to be a condition which requiredvery prompt treatment and by someoneexperienced in its management. Thisechoes modern ideal standards and yetuveitis specialists and patients still fre-quently report very late or missed dia-gnosis and inappropriate or no referral.

The next paragraph of interest seems todescribe the clinical picture closely. Thisappears accurate even compared tomodern knowledge and it does demon-strate the importance held at that time ofdifferentiating the diagnosis from otherconditions such as conjunctivitis.

“Symptoms: The eye is red and pain-ful, the pain frequently shooting abovethe eye and into the nose. The rednessdiffers from that of conjunctivitis inthat it is most intense round the "sight"of the eye, there frequently being anintense purplish-red halo around it.The pupil is usually smaller than thatof the other eye, and often irregular


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Patient Groups & Information


uveitis

Patient Groups & Information

Uveitis Information GroupA patient led information and support group.

Activities- Provision of information and support by letter, phone and email.- Public meetings around the UK.- Web site

To Contact:POST: UIG, South House, Sweening. Vidlin, Shetland Isles, ZE2 9QEEMAIL: [email protected]: www.uveitis.net

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uveitis appears once a year – in German, French and English languageFree for members of the national uveitis patient interest groups

Circulation: 4300 copies for the English edition (in total 26.000 copies)

Editor for the English version: Uveitis Information Group

Contact: Phil Hibbert, South House, Sweening. Vidlin, Shetland Isles, ZE2 9QE

Phone: +44 (01806) 577310 Email: [email protected] Website: www.uveitis.net

Overall Editor: Manfred Zierhut

Editorial Office: Jutta Grimm, Phil Hibbert, Matthias Nahm, Chris Parkin,Carlos Pavesio, Chris Rodgers, Manfred Zierhut

Cheques may be payable to Uveitis Information Group.Outside the UK, please contact the UIG.

Articles in this journal reflect the opinions of the authors and not necessarily of theeditorial office.


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