Phenothiazines Amiodarone Digoxin Plaquenil Dilantin (Phenytoin) Topamax (Topirimate) Fosamax

Tamoxifen (Nalvodex) Isoretinoine (Accutane) Viagra/Levitra/Cialis Cidofovir Voriconazole (Vfend) Interferons Flomax

	URL: http://www.opt.indiana.edu/ce/syspharm/part2.htm Revised: June 23, 2009
	IU Optometry home page: http://www.opt.indiana.edu/ Comments (content): Dr. Brad Sutton at brsutton@indiana.edu Comments: Web Administrator Copyright © 2009, The Trustees of Indiana University

Decreased accommodation, dry eye, anterior subcapsular (ASC) cataracts, corneal endothelial pigment deposits, and macular pigment changes can be side effects of oral phenothiazines (Thorazine, Mellaril). Macular pigment changes are sight threatening; cornea and lens changes have little impact on vision. Macular pigmentary changes are rare with Mellaril (Thioridazine)and are more commonly encountered with Thorazine (chlorpromazine). Other more common meds like Prozac and Zoloft affect accommodation and cause dry eye. Phenothiazines are older medications, and their use is diminishing considerably.

Antiarrhythmic agent (K+ channel blocker) Cardarone or Pacerone Half life of up to 100 days! Vortex keratopathy: Almost universal after six months or more of therapy Does not typically have a major impact on vision. Resolves months after therapy is discontinued. Can also rarely affect color vision Amiodarone also causes bilateral optic nerve head edema in 2% of patients Mimics NAION but occurs in both eyes VA changes slowly recover and often return to baseline norms after discontinuing the drug, but VF changes may not

(click image for larger view)

Optic neuropathy

Digoxin is a cardiac agent used for atrial fibulation/flutter and congestive heart failure (CHF). If doses exceed standard therapeutic levels, 95% of patients develop ocular complications.

• The most common ocular side effect is color disturbance . . . often taking the form of a gold or yellow tinge to images
• Haloes and other color changes are possible
• Rare ocular side effects include:
  • Optic neuritis
  • Loss of central vision
  • Decreased acuity

Hydroxychloroquine (plaquenil) is one of the most common reasons for routine ocular screening for adverse reaction. It is used for treatment of rheumatoid arthritis (RA) and Lupus.

Chloroquine (Aralen) is used as an antimalarial drug; very rarely for RA and Lupus. There is a much greater chance of ocular damage. It is rare to be on long-term therapy with Chloroquine.

Some patients take Plaquenil 200 mg/day, but many are on 400 mg/day. It is usually prescribed in 200 mg tablets.

Risks for ocular damage include:

• Obesity (adipose cells can not store the medication so more is available to cause macular toxicity)
• Low body weight/daily dose over 6.5 mg/kg
• Renal or hepatic dysfunction
• Extended duration of therapy
• Lifetime dose over 200 g

If patients are on 200 mg/day, ocular problems are very rare. At 400mg/day for extended periods of time, the risk is much greater. Ocular damage and symptoms can progress after meds have been discontinued. Damage can be irreversible.

Ocular side effects of Plaquenil: Bull's eye pigmentary maculopathy Visual field loss Decreased vision and contrast sensitivity Color vision changes

Bull's eye maculopathy

Bull's eye IVFA

Plaquenil Management Testing should include: Visual acuity Amsler grid (red on black may be more sensitive) Central visual field analysis with 10-2 threshold VF Color vision testing including blue/yellow (Waggoner, extended Ishihara) Dilated evaluation of macula Multifocal ERG (very sensitive!) when needed Report to rheumatologist Discontinue when possible at earliest sign of trouble (remember can progress after d/c)

Chloroquine maculopathy

Plaquenil Follow-Up

If no problems and on 200 mg/day, patient can be seen yearly. If on 400 mg/day, see patient every 6 months if no problems, more frequently if issues arise. Communication with the prescribing physician is the key!

Dilantin is an anticonvulsant used to treat seizures/epilepsy. Ocular side effects include: Blue-yellow color disturbance Nystagmus Diplopia Rarely ophthalmoplegia Nystagmus and color disturbances are relatively common and are dose related. Perform standard eye exam with addition of blue/yellow color testing. Report problems to the patient's neurologist.

An anticonvulsant used for migraines, epilepsy, depression, bipolar disease, and weight loss--Topamax carries an FDA warning for ocular side effects. Topamax can cause uveal effusion with swelling of the ciliary body leading to pupillary block and angle closure. Excessive myopic shift can also be seen. Occurs most often within 2 weeks of instituting treatment. Nearly 100 cases of acute angle closure have been reported to the FDA. This can also happen with other sulfonamide drugs but it is very rare. LPI is ineffective. Treatment consists of discontinuing the drug and utliizing cycloplegics and steroids to decrease the uveal effusion.

Narrow angle with iris bombe

Fosamax is a biphosphonate used to treat osteoporosis. It is also used, although rarely, to treat Paget's disease and bone metastases. Ocular side effects include scleritis . . . and rarely iritis, conjunctivitis, ptosis, yellow color disturbance, and diplopia.

Tamoxifen retinopathy

Tamoxifen is an anti-estrogen therapy (similar in chemical structure to chloroquine) used for the management of breast cancer. Ocular side effects are found in 6% of those using Tamoxifen. It causes a crystalline retinopathy and can also cause vortex keratopathy and macular edema with decreased vision. It can also cause astrocyte swelling leading to decreased optic cup volume. Report to oncologist/physician. Monitor yearly.

Isoretinoine is used to treat acne. Ocular side effects include:

• Dry eyes/meibomian gland dysfunction
• Conjunctivitis
• Decreased night vision

Rare ocular side effects include corneal deposits, color vision disturbances, acute myopic shifts, and increased intercranial pressure (ICP) leading to papilledema.

Viagra, Levitra, and Cialis are Phosphodiesterase 5 (PDE 5) inhibitors and are prescribed for erectile dysfunction (ED).

PDE 6 is found in the retina and while these drugs work on PDE 5, they have some effect on PDE 6 (10 times more effect on PDE 5). Changes in color perception are common (many colors possible). Increased light sensitivity as well as photopsia can occur. Ocular side effects are dose dependent: those taking 200mg of Viagra have a 50% chance of ocular side effects; 50 mg (normal dose), less than 5% chance.

There are reports of non-arteritic ischemic optic neuropathy (NAION) developing within 24-36 hours of taking Viagra and Cialis (around 50 cases have been reported to the FDA). All individuals involved had a "disc at risk" and vascular risk factors for NAION. These vascular problems are common in those suffering from ED.

Patients with a history of myocarpial infarction have 10 times the risk of developing NAION while using these agents; those with hypertension have 7 times the risk. The risk is much higher in Viagra and Cialis users than in Lipitor users. Theoretically, individuals taking Lipitor should have similar risk factor profiles for NAION as those using Viagra and Cialis. Perhaps these medications add to the risk for individuals already at high risk for the development of NAION.

Cidofovir is an antiviral agent used to treat cytomegalo virus (CMV). Roughly 25% of patients develop iritis several days after IV infusion; more common in "sicker patients."

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Voriconazole is an antifungal drug that affects PDE 6 in the retina, so it has many of the same ocular side effects as Viagra, etc. Color vision changes, photophobia, and blurred vision can occur 30 minutes after dose. There is no link to NAION.

Interferons are used to treat multiple sclerosis, hepatitis, and other viral diseases. Treatment of hepatitis with pegulated interferon is becoming more frequent. The most common ocular side effect is retinal cotton wool spots (CWS) near the optic nerve, but hemorrhaging and macular edema can occur. Follow thorough course of treatment and correspond with prescribing physician. IMAGES: Interferon retinopathy. Note cotton-wool spots.