MIDWEST UVEITIS SOCIETY

FOR SCIENCE AND EDUCATION

MUSE

March 2011

Review of:

AUS meeting – Florida 2011

Wanda M. Martinez, MD, PhD

Eye Institute

Medical College of Wisconsin

Uveitic Macular Edema:

From Bench to Bedside

Risk Factors for Uveitic Macular Edema

UME seen in 20-30% of all patients w uveitis

More common in intermediate and panuveitis

Risk factors for developing CME

Age

Duration of disease (18% 1yr, 30% 5yr)

Smoking

worse for panuveitis and intermediate uveitis.

1.5 risk of mortality if uveitis and smoking

Increased risk of bilat inflammation, reduced vision,

increased risk of recurrence, median time to

recurrence shorter

Uncontrolled inflammation but also controlled

inflammation if attached hyaloid and VMT

Janet L. Davis, MD

Bascom Palmer

Conventional and Novel Methods of

Diagnosis of UME

Advantages of fluorescein angiography:

distinguish cystoid degeneration vs edema

compared to OCT,

detection of vasculitis

Infrared SLO (scanner laser ophthalmoscopy)

modest correlations between cyst areas and visual

acuity; but can not see small lesions.

Predictors of visual recover

integrity of ELM can predict visual recovery,

outer segments may “re-elaborate”

New imaging modalities: swept source and

OCT bio-microscopy

SriniVas Sadda

Doheny Eye Center, LA

Therapy for Uveitic Macular Edema

Russell W Read MD PhD

Univ of Alabama at Birmingham

“Pharmacological Targets for Uveitic

Macular Edema”

Thomas Albini MD

Bascom Palmer

“Intraocular Treatments for Uveitic

Macular Edema”

Therapy for Uveitic Macular Edema

Target for treatment of uveitic macular edema is

inflammation itself.

Not good animal model of uveitic macular edema.

Therapy for Uveitic Macular Edema

• Are all macular edema the same? uveitis, diabetes, vein

occlusion, med-induced, post-op, tumor.

• Are all UME the same?

• 3 patterns: diffuse macular, cystoid macular, serous

retinal edema.

• Treat macular edema:

• Prevent outflow of fluid vs. improve outflow from retina

• Main target to improve outflow is RPE

• Carbonic anhydrase inhibitor

Therapy for Uveitic Macular Edema

PROS CONS

Target is RPE Systemic side effects

Increases sub-retinal fluid absorption Not as effective in chronic CME

Visual acuity may not improve

Does not control inflammation

Toxic in animal models if delivered intravit

Somatostatin – inhibitory hormone

expression of hormone and its receptors in many ocular

structures including the retina.

has a positive effect on apical-basal direction-oriented fluid

transport in the RPE

Therapy for Uveitic Macular Edema

Missotten T (2007)A J Ophthalmol

CME reduction in 70% p monthly IM injections.

63% recurred p cessation.

Success related to duration of CME.

Therapy for Uveitic Macular Edema

STEROID TREATMENT

IVTA

55% VA improved, 5% VA unchanged, 15% VA decline

25% regress post treatment

Retisert

86% reduction of CME at 1 year, 73% at 3 yrs

side effects: 75% IOP lowering drops, 40% IOP surgery

93% cataract surgery

Therapy for Uveitic Macular Edema

STEROID TREATMENT

Ozurdex (Dexa intravit implant)

Insert info(week 8-26):

47% tx vs. 12% sham reached vitreous haze score of zero

43% tx vs. 7% sham had 3 line improvement of BCVA

7.1% tx vs. 4.2% sham had IOP >25mmHg

15% tx vs. 7% sham had cataract

Mapracorat – topical steroid – phase III trial for the

treatment of inflammation following cataract surgery.

Therapy for Uveitic Macular Edema

NSAIDS

• Oral indomethacin not effective

• Intravit indomethacin

• no retinal toxicity by histology

• rapid clearance from the vitreous

• pilot study of one intravit injection (CME due to many

etiologies)

• 8 weeks: 70% improved, 10% worsened, 20% no change

Therapy for Uveitic Macular Edema

TNF-ALPHA INHIBITORS

• Infliximab IV for chronic UME

• Ave macular thickness improved by 50%

• VA improved

• Intravitreal delivery:

• Adverse effects in AMD and DME

• Intravit Etanercept for DME

• worsening of fluorescein leakage

• Other studies:

• ESBA105 for topical administration

• Humira didn’t work

Therapy for Uveitic Macular Edema

VGEF INHIBITORS

• Bevacizumab

• 7 pt w UME (q1month inj x 3 then prn) – ave 2.5 line gain and

357mm decrease retinal thickness

• Study comparing IVK vs IVB – no difference in CFT or VA but

IVK sustained effect

• Pegaptanib

• no results ?

Therapy for Uveitic Macular Edema

Pros Cons

Minimal toxicity Does not control inflammation

Short duration / need for re-injection

PROTEIN KINASE C INHIBITORS

Ruboxistaurin – Efficacy for DME.

FDA approval after further clinical trials.

Hepatotoxicity?

Therapy for Uveitic Macular Edema

INTERFERON ALPHA 2A

complete resolution and able to taper in 62%

not effective via topical administration

contradictory results when use for Hep C tx

Therapy for Uveitic Macular Edema

Research focus: Investigations into the formation and loss

of the blood-brain and blood-retinal barrier in normal

vascular biology, diabetes and cancer

David A. Antonetti PhD –

Univ of Michigan Kellogg Eye Center

• Blood-retinal barrier is different from other vessels in the

body. Tight barrier – junctional complex.

Pathophysiologic mechanisms

of uveitic macular edema

Occludin localizes with endosomal antigens after

treatment with VGEF

Pathophysiologic mechanisms

of uveitic macular edema

Hydrocortisone decreases the permeability of a cell

monolayer to labeled solutes

Pathophysiologic mechanisms

of uveitic macular edema

Pathophysiologic mechanisms

of uveitic macular edema

Steroids increases occludin

content

Steroids increases occludin

staining at the cell border

Occludin promoter activity is increased with

glucocorticoid treatment

Pathophysiologic mechanisms

of uveitic macular edema

Pathophysiologic mechanisms

of uveitic macular edema

• TNF also disorganizes occludin.

• Dexamethasone blocks TNF-induced increased

permeability.

Free papers

Scale for Photographic Grading of Vitreous Haze in

Uveitis. (2007) Am J Ophthalmol 150(5):637-641.

Grading of vit haze, Nussenblatt 1985 – 6 grades (0-4+)

Cons: Demonstrating a 2-level change is difficult and

commonly used in clinical trials to determine efficacy

Not validated for use with photographic images

Uveitic Macular Edema

AUS Meeting Florida 2011

TAKE HOME POINTS

Need to counsel uveitic patients on smoking cessation

Need for more research on the characteristics of UME

Need for continued molecular research for new targets in

the various pathways associated with UME

Therapeutic strategies – using combination therapy

Consider aggressive treatment to prevent retinal changes

that decrease opportunity of visual recovery

Consensus on the use of nomenclature for research

purposes – vitreous haze scale

MIDWEST UVEITIS SOCIETY

FOR SCIENCE AND EDUCATION

MUSE

March 2011