Fig. 26.11 Color photograph of canthaxanthine retinopathy. Prominent perifoveal punctate yellow deposits in a doughnut-shaped ring surrounding the macula (findings were bilateral)

Toxicity Without Fundus Changes

Cardiac Glycosides

The first published report associating xanthopsia with foxglove (Digitalis purpurea) was published in 1785 [42]. Modern cardiac glycosides, including digoxin (Lanoxin, GlaxoSmithKline, Brentford, Middlesex, UK), are associated with the same toxicity. Visual acuity may be reduced, and color vision is usually diminished. The examination is typically normal, but the full-field ERG shows characteristic and reversible abnormalities [43].

Phosphodiesterase Inhibitors

The phosphodiesterase (PDE) inhibitors sildenafil (Viagra, Pfizer, Inc., New York, NY), tadalafil (Cialis, Lilly, Indianapolis, IN), and vardenafil (Levitra, Bayer, Leverkusen, Germany) are widely used to treat erectile dysfunction. These agents inhibit PDE-5 in the penile corpora cavernosa but also act against PDE-6 in the photoreceptors [44]. A single therapeutic dose may cause reversible dyschromatopsia with full-field and multifocal ERG changes [45, 46]. Typically, the fundus examination is normal, but these agents are infrequently associated with retinal vascular occlusion [47], nonarteritic anterior ischemic optic neuropathy (NAION) [48], and other objective findings. A recent review of clinical trials data reported no statistically significant association between PDE inhibitor use and NAION or

other adverse ocular events [49]. Long-term PDE inhibitor use typically causes no permanent visual loss [50], but patients with preexisting retinal disease may be at increased risk [51].

Toxicity with Retinal Edema

Methanol

Methanol has no indications for internal use, but is occasionally abused as an intoxicant or during a suicide attempt. Methanol ingestion is associated with severe visual loss, associated initially with retinal and optic disk edema, progressing to optic atrophy [52–54].

Toxicity with Retinal Vascular Changes

Talc

Magnesium silicate (talc) is used as a vehicle in the manufacture of many oral medications. Occasionally, patients abuse these medications by dissolving them and injecting them intravenously. When this occurs, talc enters the systemic vascular system and may enter the retina. Initially, small talc particles will traverse the pulmonary capillary network and enter the arterial system (Fig. 26.12). Chronic injection of talc may cause arteriovenous shunt formation in the lungs, so even relatively large talc particles may enter the retinal circulation [55, 56].

Initially, talc emboli may be asymptomatic [57], but repeated exposure may lead to a relatively typical ischemic retinopathy with capillary nonperfusion, microaneurysms, cotton-wool spots, and eventually retinal neovascularization [58–60].

Oral Contraceptives

Oral contraceptives are associated with retinal thromboembolic events, including retinal vascular occlusions [61] (Fig. 26.13). These complications