This document summarizes a meeting on uveitic macular edema (UME). It discusses risk factors for UME such as age, disease duration, smoking, and uncontrolled inflammation. Imaging techniques for diagnosing UME like fluorescein angiography, infrared scanning laser ophthalmoscopy, and optical coherence tomography were reviewed. Current and experimental therapies for UME were also covered, including intravitreal steroid implants, anti-VEGF agents, NSAIDs, TNF-alpha inhibitors, and protein kinase C inhibitors. Research on the molecular mechanisms of the blood-retinal barrier breakdown in UME was presented. The take home points emphasized counseling patients on smoking cessation, the need for more UME research, and using

1. MUSE
MIDWEST UVEITIS SOCIETY
FOR SCIENCE AND EDUCATION
March 2011

2. Uveitic Macular Edema:
From Bench to Bedside
Review of:
AUS meeting – Florida 2011
Wanda M. Martinez, MD, PhD
Eye Institute
Medical College of Wisconsin

4. 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
Janet L. Davis, MD
 worse for panuveitis and intermediate uveitis.
Bascom Palmer
 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

5. 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
SriniVas Sadda
Doheny Eye Center, LA  integrity of ELM can predict visual recovery,
outer segments may “re-elaborate”
 New imaging modalities: swept source and
OCT bio-microscopy

6. 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”

7. Therapy for Uveitic Macular Edema
 Target for treatment of uveitic macular edema is
inflammation itself.
 Not good animal model of uveitic macular edema.

8. 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.

9. Therapy for Uveitic Macular Edema
• Treat macular edema:
• Prevent outflow of fluid vs. improve outflow from retina
• Main target to improve outflow is RPE
• Carbonic anhydrase inhibitor
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

10. Therapy for Uveitic Macular Edema
 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

11. 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.

12. 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

13. 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.

14. 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

15. 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

16. Therapy for Uveitic Macular Edema
VGEF INHIBITORS
• Bevacizumab
Pros Cons
Minimal toxicity Does not control inflammation
Short duration / need for re-injection
• 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 ?

17. Therapy for Uveitic Macular Edema
PROTEIN KINASE C INHIBITORS
 Ruboxistaurin – Efficacy for DME.
 FDA approval after further clinical trials.
 Hepatotoxicity?

18. 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

19. David A. Antonetti PhD –
Univ of Michigan Kellogg Eye Center
 Research focus: Investigations into the formation and loss
of the blood-brain and blood-retinal barrier in normal
vascular biology, diabetes and cancer

20. Pathophysiologic mechanisms
of uveitic macular edema
• Blood-retinal barrier is different from other vessels in the
body. Tight barrier – junctional complex.

21. Pathophysiologic mechanisms
of uveitic macular edema
 Occludin localizes with endosomal antigens after
treatment with VGEF

22. Pathophysiologic mechanisms
of uveitic macular edema
 Hydrocortisone decreases the permeability of a cell
monolayer to labeled solutes

23. Pathophysiologic mechanisms
of uveitic macular edema
 Steroids increases occludin
content
 Steroids increases occludin
staining at the cell border

24. Pathophysiologic mechanisms
of uveitic macular edema
 Occludin promoter activity is increased with
glucocorticoid treatment

25. Pathophysiologic mechanisms
of uveitic macular edema
• TNF also disorganizes occludin.
• Dexamethasone blocks TNF-induced increased
permeability.

26. 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

27. 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

28. MUSE
MIDWEST UVEITIS SOCIETY
FOR SCIENCE AND EDUCATION
March 2011