Monday, October 27, 2014

Fingolimod, and macular edema: pathophysiology, diagnosis and management

Cugati S. et al.  Neurology Clinical Practice, October, 2014

Review article


1. Mechanism is drug acts of S1P3 receptor as agonist, reducing the tight junction between the endothelial cells of the retinal capillaries. Fluid accumulates in outer plexiform layer and the inner nuclear layer resulting in swelling of the Muller cells of retina.

2.  OCT is recommended at baseline, 3,6, months and then annually.  LATE  onset ME (>12 mo) HAS BEEN REPORTED

3. Risk is increased in  diabetic, h/o uveitis, undergoing surgery eg. cataracts

4. Treatment is stopping drug; anti-inflammatory medications can be used

5.  The BRB (blood retinal barrier) , located in the retinal pigmented epithelium and retinal capillaries, can also be injured by VEGF, angiotensin 2thiazolidinediones (rosiglitazones, pioglitazeones), taxanes (docetaxol, paclitaxel), tamoxifen, niacin, and interferons.  Ocular drugs can cause ME including PG analogues (latanoprost, bimatoprost, travopost), epinephrine, beta blockers (timolol, betaxolol) and mechanical factors such as vitreomacular traction

6.  ME was more common in MS patients with previous optic neuritis

7.  Proposed mechanism is focal intraretinal microglial activation and inflammation resulting in retinal neuronal and axonal injury AND  breakdown of the BRB, which may occur in conjunction with breakdown of the blood brain barrier.

8.  Risk of ME is dose dependent; in pivotal trials the  risk on the 1.25 dose was 1- 1.6 %; among those on the 0.5 mg dose it ranged from 0-0.5 %, 

9.  Age > 41 is an additional risk factor. 

10. Clinical presentation can include reduced vision, contrast sensitivity, and altered color vision; occasionally metmorphopsia or micropsia, or relative or absolute scotoma.  Diagnosis without OCT can be made from dilated fundus exam  with slit lamp or contact lens; findings include elevation of retinal, intraretinal cysts as an altered light reflex esp. with green light, and late fluorescein leakage. 

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