Ophthalmology

Neuro-ophthalmology questions for the week: Oral Multiple Sclerosis Therapy

Posted 11:24 AM, June 6, 2012, by tcooper

Questions:

A.  What adverse ophthalmologic reaction is associated with fingolimod therapy?
1. Optic neuritis
2. 6th cranial nerve palsy
3. Macular edema
4. Retinal detachment

B.  Which ophthalmic diagnoses make fingolimod associated macular edema more likely?
1. Arthritis
2. Uveitis
3. Hypertension
4. Diabetes


C.  What ophthalmologic screening should be done when fingolimod is prescribed?
1. A comprehensive ophthalmologic examination
2. Humphrey visual fields
3. Fluorescein angiography
4. Fundus photography



Questions and Answers:

A. What adverse ophthalmologic reaction occurs with
fingolimod therapy?
1. Optic neuritis
2. 6th cranial nerve palsy
3. Macular edema
4. Retinal detachment
Correct answer: 3. Macular edema
The incidence rate for macular edema is 0.5-1% at the 0.5 mg/day dose, the usual dose of fingolimod for relapsing forms of multiple sclerosis.
Fingolimod associated macular usually develops within 3-4 months of initiation of therapy.
Most patients with fingolimod associated macular edema have minimal or no symptoms (68%).
Symptoms include blurred vision, tinted vision and metamorphopsia.
Fingolimod associated macular edema is often very subtle on ophthalmologic examination.
Ocular coherence tomography readily demonstrates the macular edema usually with intraretinal cysts.
Fluroescein angiography demonstrates leakage within the macula.
Fingolimod associated macular edema macular edema and its associated symptoms generally resolve within a few months after discontinuation of therapy in a large majority of cases. In a few cases fingolimod associated macular edema is reduced but persists.
Macular Edema Associated with Fingolimod. Jann N, et al. EyeNet AAO Pearls-2012

Fingolimod-associated macular edema: Incidence, detection, and management.  Jain N, Bhatti MT. Neurology. 2012 :78(9):672-80.

B. Which ophthalmic diagnoses make fingolimod associated macular edema more likely?
Which ophthalmic diagnoses make fingolimod associated macular edema more likely?
1. Arthritis
2. Uveitis
3. Hypertension
4. Diabetes
Correct answers: 2. Uveitis & 4. Diabetes
Fingolimod induced macular edema is more common in patients with a history of diabetes mellitus or uveitis. A history of uveitis was present in 25% of patients who developed fingolimod associated macular edema. In studies where fingolimod was used at a 5-10 fold higher dose, 30% of diabetics developed macular edema. Fingolimod has been shown to have secondary effects on vascular endothelial barrier function, thereby potentially compromising the blood-retina barrier.

C. What ophthalmologic screening should be done when fingolimod is prescribed?
1. A comprehensive ophthalmologic examination
2. Humphrey visual fields
3. Fluorescein angiography
4. Fundus photography
Correct answer: 1. A comprehensive ophthalmologic examination
A comprehensive ophthalmologic examination should be performed prior to fingolimod therapy, whenever symptoms develop, at 3-4 months after treatment initiation, at 6 months and then annually. More frequent examination is warranted in patients with diabetes or a history of uveitis. For the first 3-4 months, daily self-screening with an Amsler grid for distorted vision is appropriate especially for patients with diabetes or a history of uveitis.

An FDA-approved patient medication guide must be dispensed with this medication.
http://www.pharma.us.novartis.com/product/pi/pdf/gilenya_pmg.pdf
Reference:
Macular Edema Associated with Fingolimod. Jain N, Bhatti T. EyeNet 2012

Two large phase 3 clinical trials have shown the beneficial effect of fingolimod in relapsing-remitting MS. In the FREEDOMS trial, 1,272 patients were randomized to treatment with 0.5 mg/day fingolimod, 1.25 mg/day fingolimod or placebo for 24 months.1 The annualized relapse rate was 0.18, 0.16 and 0.40, respectively.

In the TRANSFORMS trial, 1,292 patients were randomized to treatment with 0.5 mg/day fingolimod, 1.25 mg/day fingolimod, or once-a-week intramuscular interferon-1a (Avonex) for 12 months.2 The annualized relapse rate was 0.16, 0.20 and 0.33, respectively. In both studies, the MRI findings supported the beneficial effects of fingolimod in reducing disease activity in the brain.


RAPID ONSET. A 56-year-old female with a history of MS and bilateral uveitis recently switched from natalizumab to fingolimod. Within one week of starting fingolimod, she reported blurred vision in her right eye. The ophthalmic examination revealed a visual acuity of 20/40, with macular edema confirmed by OCT.



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