Toxic Retinopathies

Chloroquine Retinopathy
Excessive ingestion of chloroquine causes diffuse retinal deterioration. Traditionally, the
damage was thought to be caused by progressive binding of chloroquine by melanin in the RPE
cells, but later evidence indicated that the ganglion cells are also directly damaged. The
cumulative dose of drug is the most important predictor of retinopathy. Less than 100 g causes
no toxicity. When it is greater than 300 g, 70% of patients manifest some signs of toxicity.
Plaquenil (hydroxychloroquine) retinopathy is similar to chloroquine retinopathy, but
Plaquenil is much less toxic. Plaquenil toxicity is rarely seen with a total dose of less than 700 g
or an average daily dose of 400 mg or less.

Clinical Features
The earliest signs of retinopathy are small scotomata on visual field testing, a
supranormal EOG, an abnormal photostress test result, and decreased color vision. Because
visual acuity is typically affected later, it cannot be relied on to detect early toxicity. Similarly, in
an eye with early toxic reactions, the fundus may be normal. The earliest fundus abnormalities
are small areas of depigmentation of the RPE (Fig. 4.65). By the time the classic bull's-eye
maculopathy is evident (Fig. 4.66), considerable damage has been done.
The end-stage fundus appearance of chloroquine retinopathy resembles a bull's-eye pattern. The
most common causes of a bull's-eye are Stargardt's disease, cone dystrophy, and AMD.

Management

The only treatment is to discontinue the drug. Although

many patients have some recovery of vision, a few have
damage that continues to progress.
Thioridazine Toxicity

There are two types of thioridazine (Mellaril) toxicity. In the acute form, large doses
(e.g., 2,000 mg/day or more) are administered to psychotic patients, who experience an acute
decrease in central vision. In the chronic form, patients who take thioridazine for long periods at
lower doses (800 to 1,000 mg/day) have peripheral visual field loss, but they usually retain good
central vision.
Clinical Features

The acute type of thioridazine toxicity is characterized by widespread stippling of the

RPE, which includes the macula (Fig. 4.67A). In the chronic type, there are circumscribed areas
of RPE loss (Fig. 4.67B).

Figure 4.67. A: Posterior pole pigment epithelial atrophy in

a patient with Mellaril (thioridazine hydrochloride) retinopathy. B:
An equator-plus photograph shows multiple large areas of
pigment epithelial atrophy.
In the acute type, the diagnosis is usually easy because of the
history of ingestion of massive doses of thioridazine. The
chronic type may resemble gyrate atrophy. The main
difference is that the areas of atrophy in thioridazine toxicity
are not as pronounced as those in gyrate atrophy.
Management

The drug must be discontinued with any signs of

retinal toxicity.
Talc Retinopathy
In chronic intravenous drug abusers, talc particles gradually occlude pulmonary
capillaries. Pulmonary shunts develop, allowing particles to gain access to the systemic
circulation and to the eye, where they occlude retinal capillaries.

Clinical Features

In most cases, the refractile particles can be seen in the macula (Fig. 4.68). Macular
capillary occlusions cause hypoxia and edema with decreased vision. Widespread areas of
capillary nonperfusion in the periphery can lead to peripheral and optic disc neovascularization
and to vitreous hemorrhage.
Proliferative talc retinopathy must be differentiated from other causes of peripheral
neovascularization, such as diabetes, sarcoidosis, and Eales disease. Talc maculopathy can
resemble radiation and diabetic retinopathies. The patient's history and recognition of the talc
particles are important. The differential diagnosis of crystalline retinopathy in general includes
canthaxanthine, tamoxifen, nitrofurantoin, primary and secondary oxalosis, cystinosis, and
Bietti's disease.

Management
Patients with neovascularization and vitreous hemorrhage should be treated with
photocoagulation.
Tamoxifen Retinopathy
Tamoxifen retinopathy is a rare form of crystalline retinopathy occasionally seen in
patients taking the drug for extended periods of time.

Figure 4.68. Multiple talc particles

are present in the macula of a
patient who was a longstanding
intravenous drug abuser.

Clinical Features

Examination reveals subtle, yellow-white dots in the central macula with or without
vision loss or other evidence of visual dysfunction. Corneal opacities and optic neuropathy have
also been reported.
Management
The drug should be discontinued at the first signs of any visual dysfunction.