Case 7

Chief complaint
A 25-year-old female noted flashing light and subtle blurring of side vision OD for 2 weeks.

History
Past ocular history: Past optic neuritis attacks; intermittent nystagmus and diplopia.
Medical history: Multiple sclerosis for 4 years with interferon beta-1 treatment for 1 year to prevent MS attacks.

Exam

	OD	OS
Best corrected visual acuity:	20/20	20/20
Slit lamp:	unremarkable
Extraocular muscles (EOM):	full with no obvious nystagmus
Dilated fundus exam (DFE):	Cotton wool spot OD.

Assessment:

Cotton wool spot (CWS) retinopathy OD.   Etiology? Is CWS retinopathy related to interferon treatment?

Plan/Treatment

• Follow-up dilated fundus exam in 1 month.
• Inform neurologist.

Interferon-associated retinopathy: Interferons are a group of naturally occurring proteins and glycoproteins which have antiviral, antineoplastic, and immune-regulation properties. They are administered subcutaneously or intramuscularly 1 to 3 times per week. Ribavirin PO is used in conjunction to increase effectiveness. Interferon alpha is used to treat Hepatitis B and C and cancer; interferon beta is used to treat MS. The most common systemic side effects are flu-like symptoms. Interferon may cause retinal complications as well--and more often than other systemic medication (e.g., hydroxychloroquine or phenothiazines). It may cause vision loss. Some reports state up to 57% of patients taking interferon experience retinopathy (first reported in US in 1993). The two most common signs with interferon-related retinopathy are cotton wool spots and retinal hemorrhages. They are usually found at the posterior pole around the optic nerve head. Unilateral or bilateral. They typically occur within 1 to 3 months of treatment which makes it important to see patient for a baseline exam at the beginning of interferon treatment. Cotton wool spots and retinal hemorrhages normally spontaneously resolve during or after treatment. Supposedly there is no difference in incidence with alpha or beta, but there are many more reports with alpha. Rarer eye findings Impaired vision Retinal artery/vein occlusions Bilateral oculomotor nerve paralysis Mydriasis Anterior ischemic optic neuropathy Microaneurysms Subconjunctival hemorrhages Vascular tortuosity and congestion Early onset of cataracts Vitreous hemorrhage CME Photophobia Ocular side effects are more likely if patient . . . Also has diabetes mellitus, hypertension, or anemia Is older, female, or has arterial sclerosis Is on higher dose of interferon Is also taking antidepressant medication paroxetine (a serotonin-reuptake inhibitor) Why is this damage occurring? The exact mechanism is unknown. Possibilities include the occlusion of retinal vessels due to deposition of immune complexes related to activation of complement. Direct damage of the vessel walls may be caused by the medication itself or by Hepatitis C virus. Damage may be due to increased viscosity of the blood. So, what should be our standard of care? Patient should receive baseline fundus exam before starting interferon treatment. Inform the MD. Let physicians know that patients need to be monitored closely. Patient should be followed every 3 months. Take fundus photos to monitor for progression. Give patient Amsler grid for home monitoring. Instruct patient to return ASAP if notes any changes in vision. If sight is threatened, contact patient's MD to weigh the risks/benefits of discontinuing the medication.

Summary

• Interferon alpha (Peg-Intron/Rebetol, Pegasys/Copegus, Intron-A, Roferon-A) = Tx for hepatitis and cancer.
• Interferon beta (Avonex, Betaseron) = Tx for MS.
• Main side effects are flu-like symptoms.
• Main eye findings will be cotton wool spots and retinal hemorrhages.