Medical Treatment of UveitisRukiah Syawal Bag. I.P. Mata Fakultas KedokteranUniversitas Hasanuddin

Diagnosis and Treatment of UveitisA challenge for OphthalmologistsThe basis of intraocular inflammationImmunology, molecular biology, cell biology, other big medical scienciesRapid development new diagnostic tools clinical evaluation and therapeutic decisions

Treatment of Uveitis Considerations :Pain, Photophobia, DiscomfortDegree and location of inflammatory diseaseEvaluation of V.A and prospect of reversibilityFollow up procedures and standardizations of observation.One eye or twoGeneral health and age of patientPatient reliability, preferences and understanding INFORMED WRITTEN CONSENT

UveitisPrevalence: US and Western: 38 / 100.000. Denmark : 14 / 100.000, France : 17 / 100.000Mean age presentation : 40 years (any age)Peak age at onset: 3rd and 4th decades Socioeconomic impactA significant cause of blindness(U.S.: 10-15% of all causes of blindness due to Uveitis) Causes of blindness : maculopathies (edema, cystoids, membrane, cataract, glaucoma, hypotonic, retinopathy

Goals of TreatmentAbsolute control of inflammationNo long term steroidsNo serious drug-induced problem

Therapeutic PrinciplesPreservations of functionRisk-benefit ratioUnderstand the diagnosisClassification of UveitisUSE ENOUGH, SOON ENOUGHINFORMED CONSENT documentCo-management with other expert

THERAPY FOR UVEITIS

MEDICAL MANAGEMENT OF UVEITISCycloplegic: breaking or preventing posterior synechiaerelieving photophobia / ciliary spasmshort acting ( cyclopentolate ) : acute anterior Uveitislong acting ( atropine ) : chronic UveitisCorticosteroid:The mainstay of Uveitis therapySpecific indication :Therapy active inflammationPrevention / treatment of complications ( CME )Reduction inflammation of the retina, choroids, optic nervComplication : numerous, mode of administration

MODE OF ACTIONPoint for the action need cellular receptor at cell surface complexes with it in cytoplasm migrate to nucleus effect DNA change RNA production change in protein production and cell function

Effect of Steroid

Ophthalmic Topical Corticosteroid preparations

Relative Potencies of Corticosteroid

Administration

Topical Anterior UveitisPeriocular intermediate & posterior uveitissubconjungtivalanterior or posterior subtenontranseptalretrobulbarSystemic OralIntravenous severe, bilateral, sight threatening post Uveitis

Treatment failurePoor Patient complianceInadequate dosingAbrupt or rapid tapering scheduleSteroid induced ocular complicationLess frequent dosing low grade inflammation long term permanent ocular damage

High-Risk GroupElderly & postmenopausal osteoporosis, severe hypertension, heart failureChildren : suppress normal growthNewborn of another receive steroid growth retardation

Topical SteroidActive inflammation IMPERATIVEAGGRESSIVEEvery hour waking timeEvery 15 minutes first hour loading doseTherapy effective, every 2-3 days once a week Begin a very low tapering individualNumerous attack: 1-2 drop /day for weeks/month

Perioculary CorticosteroidSevere inflammatoryLong acting / short actingEvery 1-2 weeks for short period, repeat every 2-4 weeksUnilateral Uveitis, at time of surgery on an Uveitis eye, systemic effect of steroid should be avoided, CMEBui Quoc et all, 61 uveitis 1 0n > inflammation (periocular) triamcinolon 40 mg subtenon IOP , 52% improvement visual acuity

SECONDARY EFFECTecondary effect of periocular inj

General anesthetic for childhood Uveitispenetration of the globeProptosis and fibrosis extra ocular muscleRetinal & choroidal occlusion Severe intractable glaucomaReaction to the vehicleScleritis, ocular toxoplasmosis, steroid inhibit new collagen growth perforation

Intraocular:Intravitreal : triamcinolon 2-4 mgIntracameralFluocinolone slow release implant

SystemicInitial: severe bilateral endogenous sight- threateningGordon: Use enough, soon enough, then taper and discontinueMussemblat : 1 1,5 mg/kg/day Prednison, maintain until clinical effectReasonable time limitFoster : 1 2 mg /kg/day single dose or 4dd less than 2 weeks clinical response begin slow and steady taper until 20 mg/dayFauci : 40 mg every other day 2 weeks, taper to 30 mg every other day 2 weeksInflammation 20 mg every other day 2 weeks15 mg every other day, 10 mg, 7,5 mg, 5 mg every other day.--> zero / discontinue

Intra Venous -> alternativeSEVERE, BILATERAL, SIGHT THREATENING POST UVEITISMEDICAL EVALUATION BEFORE THERAPYMethylprednisolone 1 mg/days 3 daysOnce a month

NSAIDPost operative inflammation, CMECombine with steroid topicallyComplicationGbr 11-1 hal 168 vitale

IMMUNOSUPRESSIVEIndication:Vision threatening intraocular inflammationReversibility of the disease processInadequate response to corticosteroidcontraindication of steroid

CONSIDER THE GUIDELINESAbsence of infectionAbsence of hematologic contraindicationMeticulous follow up (ophthalmologist, internist)Objective evaluation of the disease processINFORMED CONSENT

Cyclosporine SandimmuneIndication: Active bilateral sight threatening non infection Uveitis unable to tolerate systemic corticosteroidBechetsChronic intraocular inflammationSympathetic ophthalmiaCorneal transplantDose 5 mg /kg/day (max 7mg/kg/day) 1dd1 or 2dd (combined steroid)10 mg/kg/day

CYTOTOXIC AGENTAlkylating chlorambucil, cyclophosphamideAnti metabolic azathioprine, methotrexateAlkylating: alkyletion DNA inability separate during division cell deathIndication : Bechet, severe bilateral sight threatening, endogen uveitis, intermediate UveitisSide effect: leucopenia, thrombocytopenia, anemia, testis atrophy, lungs fibrosis, renal toxic, teratogenic, vitreal impairment Antimetabolic: affect DNA and RNA metabolismINFORMED CONSENT

RESUME

TOXOPLASMOSIS79 15% from all Uveitis casesAcute sign & symptom: headlight in a fog (focal retinitis, arteritis, periphlebitis)Adequate therapy lesion healed at 3-6 weeks80% cases with retinochoroiditis

TreatmentStandard therapy :Sulfadiazin 1 gr 4dd1 orallyPyrimethamin 50 mg 2ddFolic acid 3-5 mg 3dd/weeksPrednisone 20-40 mg/day tapering!!! Steroid + antotoxoplasm if there is sight threateningAlternative:Clindamycin 150-300 mg 3-4dd orallyBactrim forte 1-2 tab 2dd

SYMPATHETIC OPHTHALMIADD with VKHEnucleation injured eye ??Enwel : NO EFFECT on sympathizing eyeBellon: enucleation 5 days after injury 3 months sympathizingLubin et all: enucleation within 2 weeksKil martin: enucleation not seen to correlate with better visual acuity outcomeBrackup et all: 50 eyes global rupture not remove within 2 weeks, later: 17 remove (BPE), 33 notremove, comfortable 66 month follow up

TreatmentSteroid (Prednison / equivalent)Innitial : 1-1,5 mg/kg/daySevere: 100-200 mg/day + IVThe next days : immunosuppressiveHow long? Frame (about 3 months)Cyclosphorine: after steroid, .cytotoxickeadaan yang berat dan bandel TRIPLE IMMUNOSUPRESSIVE (cyclosphorine, orally corticosteroid, azathioprine)Inflammatory process terkontrol tunggu paling tidak 3 bulan sebelum intervensi surgical

ENDOPHTHALMITISInflammation involving vitreous cavity & anterior chamberInfectious endophthalmitis : infectious process >>Non Infectious : Retained lens referralToxic Substance

SIGN & SYMPTOMDecrease V.A LOSSAnterior Chamber reaction / hypopionVitritisAssociated pain / pain (-)Conjungtiva hyperemia, eyelid edem

YARBROUGH :Pain is critical to diagnosisPain relief with acetaminophen (avoid narcotic analgetic)Worsening anterior chamber inflammationHypopionRedness

INFECTIOUS ENDOPHTHALMITIS

POST OPERATIVE ENDOPHTHALMITISSource of infection : eyelid, conjuctivaOrganism : Staphylococcus speciesPropionibacterium acnesONSETAcute onsetPost Operative Endophthalmitis : 1-14 daysStaphylococcus epiodermidisCoagulase negative staphylococcus >>Severe Acute Onset : 1-4 day post operativeANG ClL et all Risk factor for Endophthalmitis (SNEC)IOL : Silicone IOL > PMMA IOLOccurance of post capsular ruptureThe need to perform anterior vitrectomy

TO HELP PREVENT ENDOPHTHALMITIS (Mah. F.S.)Mechanical lid scrubsBacitracin ointmentOral DoxycyclinPre operative Povidone-Iodine 5% A week prior surgery Prior to cataract surgery : povidone-iodine on the ocular surface 5 minutes The night antibiotic (Ofloxacin, Ciprofloxacin, Levofloxacin) resistantMah. F.S. : Gatifloxacin and Moxifloxacin / 4th generation

General Consideration for TreatmentMild acute-onset post Operative : intraocular antibioticTopical antibiotic + SteroidSevere acute :Intravitreal + subconjuctiva + topical antibioticPars plana vitrectomyTopical and periocular steroid

TOXIC ANTERIOR SEGMENT SYNDROME (TASS)A sterile post operative inflammatory reactionOnset : 12-48 hoursSymptom :blurry visonpain freedevelop symptom within 24 hourswidespread limbus to limbus corneal edgemarked anterior sign inflammatory reaction, cells & flare, hypopion, fibrin reaction, dilatated or irregular pupil

DD / EndophthalmitisCauses : Intraocular solution inappropiate chemical composition, concentration, pH, osmolality, preservatives, viscosurgical device, detergent, bacterial endotoxin, oxidized metal deposit, related to IOLTherapy :Prednisolon acetate 1% every 1-2 hourClosed follow up