effects side ocular induced-Drug • 7 Part

Fig. 7.6a  Amiodarone whorl-like pattern of golden brown deposits in the anterior cornea.

Fig. 7.6b  Optic nerve pallor from amiodarone optic atrophy.

Probable

1. Loss of eyelashes or eyebrows

2. Thyroid eye disease

a.Hypothyroid ocular signs

b.Hyperthyroid ocular signs

3. Papilledema secondary to intracranial hypertension

4. Autoimmune reaction

a.Dry mouth

b.Dry eyes

c.Peripheral neuropathy

d.Pneumonitis

Possible

1. Optic neuropathy

a.Visual loss

b.Disc edema

c.Disc hemorrhage

d.Optic nerve pallor (Fig. 7.6b)

e.Visual field defects

Clinical significance

Amiodarone was first introduced in the 1960s and its most frequent drug-induced side effects are ocular. These side effects, especially in the anterior segment, are dose and time dependent.

Corneal microdeposits due to aminodarone occur in all patients who are using the drug long term. The corneal epithelial whirllike drug-related deposition is indistinguishable from that due to quinacrine, indomethacin, chlorpromazine, etc. The keratopathy may reach a steady state with no progression even with continued drug use. The usual pattern for corneal deposition (Klingele et al 1984) initially, in stage 1, is a horizontal, irregular, branching line near the junction of the mid and outer one-third of the cornea. In stage 2, this increases so that there are 6 to 10 branches, with an increase in length and curve superiorly. Any increase in the number of branches constitutes stage 3. Stage 4 is the whirl-like pattern with clumping deposits. The deposits may be seen as early as 2 weeks after starting the drug, but in general the visible keratopathy develops in most patients within 6 weeks after initiation of amiodarone therapy and reaches its peak within 3–6 months. Patients taking 100–200 mg/day have only minimal or even no visible corneal deposits. At dosages of 400 mg or more almost all patients will show corneal deposits. Once the drug is stopped most deposits completely regress in 3–7 months, but this may take up to 2 years. In patients using soft contact lenses, the keratopathy is significantly less. Visual changes due to these deposits are uncommon, but on occasion are severe enough to stop the drug. Patient complaints consist of photophobia, hazy vision or colored haloes around lights. Occasionally, a patient may complain that bright lights, especially headlights at night, will cause a significant glare problem. Keratitis sicca has been reported since the drug is secreted in tears, which may aggravate borderline sicca cases or enhance the evaporative form of sicca. A probable autoimmune reaction can occur, which is associated with dry mouth, dry eyes, peripheral neuropathy and pneumonitis. Slate-gray periocular skin pigmentation or blue skin discoloration has been seen secondary to photosensitivity reactions. Corneal ulcerations can rarely occur during treatment with amiodarone. Flach and Dolan (1990) first described subtle anterior subcapsular lens opacities in patients taking amiodarone long term. These changes primarily occur in the pupillary area and are yellow-white, loosely packed deposits that rarely interfere with vision. The location of the deposits suggests a photosensitizing effect of amiodarone on the lens. Cumming and Mitchell (1998) reported increased cortical cataracts.

Does amiodarone cause optic neuropathy? It is not known if this is simply a variant of non-arteritic ischemic optic neuropathy (NAION), in which swelling of the disc is prolonged, or if amiodarone is an independent risk factor of NAION. Regardless, from a practical point of view one may need to practice defensive medicine since the legal system has determined a relationship between amiodarone and NAION in a number of cases. Scientific data (along the guidelines of Murphy and Murphy 2005) are necessary to determine if a relationship exists or not. However, some feel amiodarone optic neuropathy is possibly characterized by an insidious onset, slower progression, which often has bilateral visual loss and protracted disc swelling. NAION may be characterized as an acute, unilateral visual loss that is usually complete at onset with resolution of disc edema over several weeks. Optic nerve swelling and peripapillary nerve fiber layer hemorrhages tend to persist for several months in amiodarone-induced optic neuropathy, while in NAION these usually resolve more quickly. After discontinuation of amiodarone, visual acuity and visual field defects tend to stabilize. Purvin et al (2006) have recently recommended (Table 7-6a) a systemic approach with well-defined diagnostic criteria to help the clinician manage these patients. Fraunfelder and Fraunfelder (2007) predict that, in time, the association of this drug causing a neuropathy will be ‘probable’. Although the mechanism of amiodarone optic neuropathy, or even if it occurs,