Dr Jean VaudauxMorges et RétinElysée, Lausanne

Diagnostic et traitement de l’œdème maculaire uvéitique

SAoO 6 mars 2019Lucerne

Introduction

• Cystoid macular edema (CME) is the first cause of visual morbidity in uveitic patients

• CME is generally a complication of intermediate or posterior uveitis, but may also be associated with anterior uveitis (HLA-B27+)

• Directly related to disruption of the inner blood-retinal barrier, i.e. tightjunctions of endothelial cells lining retinal vessels

• Role of prostaglandines, leucotriens and cytokines (IL, TNF-𝛼𝛼, VEGF)• Loss of pumping effect from the RPE• Fluid accumulates in the outer plexiform layer

Introduction

Diagnosis

• Clinical examination• Fluorescein angiography• OCT• (OCT angiography)

Diagnosis – clinical examination

• Macular thickening• Asymmetric foveal reflex, fovea looks ‟dull”• ‟Lobulated” appearance• With 78D lens or contact macular lens

Diagnosis – fluorescein angiogram

• Macular leakage, ‟petaloid pattern”; maximum leakage on late frames

Diagnosis – OCT

• Hyporeflective spaces within the outer plexiform layer, can thenstretch out across several layers of the retina

Therapy - principles

• WHEN? When should I treat?

• WHO? Which patient should be treated?

• WHAT? Which drug(s)/medication(s) should I prescribe?

• HOW? Route of administration

• HOW LONG? When should I consider discontinuing therapy?

Therapy

Therapy - WHEN

• Whenever there is decreased visual acuity (VA) and the patient complains of it

• VA threshold? 0.5?- Not determined- Consider more aggressive indication if monocular patient- Hope for visual recovery; long-standing CME often responds poorly to

therapy; if it does, sometimes no anatomical-functional correlation

Therapy - WHO

• Depends on type of uveitis and anticipated outcome- Infectious uveitis: always treat underlying infectious cause (tbc, syphilis)- Pars planitis: treat all patients with CME, significant visual morbidity- Birdshot: treat all patients with CME, otherwise risk of secondary macular

atrophy• Age: adults versus children• Consider global health status, particularly in elderly people, drug

interactions; growth retardation with corticosteroids in children• Compliance: do you feel that the patient will be compliant?

Therapy - WHAT

• NSAIDs- Topical: only indicated in pseudophakic postoperative CME (Irvine-Gass)- Systemic: no role in management of uveitic CME

• Corticosteroids: mainstay of CME management- Rapid effect- Choice in the route of administration- CAVE infectious uveitis, always rule out infectious cause before treating- Consider potential side effects

Therapy - WHAT

• Corticosteroids- Topical: Irvine-Gass, but insufficient for uveitic CME- Periocular: posterior sub-Tenon’s triamcinolone 20-40 mg

CAVE: ocular hypertension, test with topical Predforte for 10 days beforeCheck IOP 2 weeks after injection

Therapy - WHAT

• Corticosteroids- Intraocular: intravitreous triamcinolone 4 mg

Short-lived, up to 40% ocular hypertension, risk of endophthalmitis

- Intraocular: drug delivery systems (DDS)Fluocinolone implant (Retisert®)Dexamethasone implant (Ozurdex®)

Therapy - WHATFluocinolone implant Dexamethasone implant

At 34 weeks follow-up:50% eyes treated for ocular hypertension6% eyes require glaucoma surgery

At 3 years, 100% eyes require cataract surgery

Study eye - implant

Fellow eye – pas d’implant

Jaffe GJ, et al. Fluocinolone Acetonide Uveitis Study Group.Ophthalmology 2006;113:1020-1027

Williams GA, et al. Dexamethasone posterior-segment drug deliverysystem in the treatment of macular edema resulting from uveitis or Irvine-Gass syndrome. Am J Ophthalmol 2010;149:550-561

Therapy - WHAT

• Systemic corticosteroids: oral- Initial dosage prednisone 1 mg/kg/day, ideal dosage max 60 mg/day- Tapering down after 2-4 weeks- Target: ≤ 7.5 mg/j- Tapering down using decrements to 1. reduce recurrence risk and 2. avoid

withdrawal (chronic long-standing oral corticotherapy)

Therapy - WHAT• Systemic corticosteroids: oral

@ 2 months, prednisone ½ mg/kg/day, VA 0.5

@ baseline, VA 0.5

@ baseline, VA 0.25

@ 3 wks, prednisone ½ mg/kg/day, VA 0.6

Therapy - WHAT

• Immunosuppressants: steroid-sparing effect, kick in usually severalweeks-

Jabs DA. Ophthalmology 2018

Mycophenolate: in one retrospective study, no recurrence of CME in 87.5% of eyes, meanfollow-up 30 months

Therapy - WHAT

• Anti-TNF𝛼𝛼- Soluble receptor: etanercept; not effective in uveitis- Monoclonal antibodies: infliximab (Remicade®), adalimumab (Humira®)

Effective in Behçet’s uveitis, HLA-B27-related and JIA-associated uveitisBirdshot, sarcoidosis, idiopathic uveitisEffective in the management of uveitic CME

Infliximab 5 mg/kg IV: study on 14 eyes/10 patients

Adalimumab 40 mg SC every 2 weeks

Markomichelakis NN, Theodossiadis PG, Pantelia E, et al. Infliximab for chronic cystoid macularedema associated with uveitis. Am J Ophthalmol 2004;138:648-650

@ 50 sec (a) before and (b) after 3 months of combined corticosteroids and ADA therapy

@ 2 min (c) before and (d) after 3 months of combined corticosteroids and ADA therapy

Therapy - WHAT

• Combination therapy- On a case-to-case basis- Generally corticosteroids (prednisone < 7.5 mg/day) + 1

immunosuppressive drug or anti-TNF𝛼𝛼- Posterior sub-Tenon’s triamcinolone as an adjunct, on a PRN basis

Therapy - HOW

• Route of administration- Topical: limited usefulness, except postoperative pseudophakic CME- Periocular: posterior sub-Tenon’s triamcinolone as an adjunct- Intraocular: intravitreous corticosteroids/anti-VEGF, as an adjunct, case-to-

case basis- Systemic

Oral: corticosteroids, immunosuppressantsIV: corticosteroids, infliximabSC: MTX (children, JIA), adalimumab

Therapy – HOW LONG

• Ideal: until complete functional and anatomical recovery (VA, OCT)• Aim: until remission is achieved• No consensus, no formal evidence, depends on many variables:

- age- type of uveitis, known prognosis and outcome- uni-/bilateral uveitis- patient’s general condition- occurrence of side effects

• Principle: min. 1 ½ - 2 yrs after complete discontinuation of steroids

Conclusions – message to take home

• Multimodal diagnosis: clinical, angiography, OCT• Mainstay of therapy = corticosteroids; aim for prednisone < 7.5 mg/day• Immunosuppressants: steroid-sparing effect, long-term therapy

- 1st choice usually antimetabolites, efficacy/tolerance• Anti-TNF𝛼𝛼: adalimumab• Posterior sub-Tenon’s triamcinolone: easy, no systemic side effects• Combination drug therapy and combined routes of administration• Treat aggressively if CME is in only eye, or bilateral and refractory• Monitor and follow-up closely, screen for recurrence

Quizz #1

What causes macular edema (only one answer)?

1. Transfer of aqueous from the anterior chamber to the outer plexiformlayer

2. Transsudation of fluid from the underlying choriocapillaris3. Disruption of the inner blood-retinal barrier4. Swelling of Müller cells5. None of the above

Quizz #2

Which of the following about CME is FALSE (only one answer):

1. Accumulation of fluid within the subretinal space2. Major cause of visual impairment in uveitic patients3. Results from disruption of the inner blood-retinal barrier4. Can be seen in anterior, intermediate, or posterior uveitis5. Petaloid pattern on fluorescein angiography

Quizz #3

Which of the following regarding corticosteroids is FALSE (only one answer):

1. Act fast2. Route of administration may be oral, periocular, topical or intraocular3. Aim for prednisone < 7.5 mg/day4. Topical prednisolone alone is rarely effective in uveitic macula edema5. Should never be used in children or very old patients

Quizz #4

72 y.o. male, recurrent HLA-B27+ acute anterior uveitis OS, what wouldyou do (only one answer)?1. Treat with topical NSAID (either Acular®, Nevanac®, or Yellox®)2. Treat with oral prednisone3. Treat with posterior sub-Tenon’s triamcinolone4. Treat with topical dexamethasone and NSAID, add acetazolamide, if

not effective consider surgery with or without Ozurdex5. Treat with intravitreous anti-VEGF

4 months post phaco OS 6 months post phaco OS