Drug-induced maculopathies

Antimalarial drugs

Chloroquine (nivaquine, avlocor) and hydroxychloroquine (plaquenii) are quinolone derivatives used in the prevention and treatment of malaria, as well as in the treatment of rheumatoid arthritis, systemic lupus erythematosus, and cutaneous lupus. Chloroquine is also recommended for the treatment of calcium metabolism disorders in sarcoidosis. Antimalarial drugs are melanotropic and are excreted from the body very slowly, which leads to their accumulation in melanin-containing structures of the eye, such as the retinal pigment epithelium and choroid. Retinotoxicity and corneal deposits are the two main ocular side effects of antimalarial drugs. Retinal changes are uncommon but potentially dangerous, while corneal changes (infundibular keratopathy), which are extremely common, are not dangerous.

1. Chloroquine retinotoxicity is related to the total cumulative dose. The daily dose is normally less than 250 mg. Cumulative doses of less than 100 g or treatment durations of less than 1 year are very rarely associated with retinal damage. The risk of toxicity increases significantly when the cumulative dose exceeds 300 g (i.e., 250 mg daily for 3 years). However, there are reports of patients receiving cumulative doses exceeding 1000 g who did not experience retinal damage. If necessary, chloroquine can be used when other drugs are ineffective.
2. Hydroxychloroquine is less dangerous than chloroquine, and the risk of retinotoxicity with its use is insignificant if the daily dose does not exceed 400 mg. The physician should recommend hydroxychloroquine instead of chloroquine whenever possible.

[ 1 ], [ 2 ], [ 3 ]

Chloroquine maculopagy

• The pre-maculopathy condition is characterized by normal visual acuity but absence of the foveal reflex. This is accompanied by the development of fine granular changes in the macula, which may be associated with moderate impairment of color vision and small scotomas on the red Amsler grid pattern. This condition is reversible if the drug is discontinued.
• Early maculopathy is characterized by a moderate decrease in visual acuity (6/9-6/12). Fundus examination reveals a subtle change in the macula characterized by central foveolar pigmentation surrounded by a zone of depigmentation (zone of retinal pigment epithelium atrophy), which in turn is enclosed in a ring of hyperpigmentation. The lesion may be better detected by FAG than by ophthalmoscopy, since foci of retinal pigment epithelium atrophy appear as a “finite” defect. This stage is reversible upon discontinuation of the drug.

1. Advanced maculopathy is characterized by a more pronounced decrease in visual acuity (6/18-6/24) and an obvious picture of macular damage of the “bull’s eye” type.
2. Severe maculopathy is characterized by a significant decrease in visual acuity (6/36-6/60) with a widespread area of retinal pigment epithelium atrophy surrounding the fovea.
3. The final stage of maculopathy is characterized by a significant decrease in visual acuity and significant atrophy of the retinal pigment epithelium with "exposure" of large choroidal vessels. Retinal arterioles may also become thinner and retinal pigment epithelium deposits may develop at the periphery of the retina.

Screening

Monitoring of patients taking hydroxychloroquine is not required. In clinical practice, chloroquine can also be safely prescribed to patients who do not need routine repeated ophthalmologic examinations or the use of complex tests. In this case, visual acuity and fundus examination are quite sufficient.

The patient can use the Amsler mesh independently once a week, and if any abnormalities are detected, he or she must be referred for an ophthalmological examination.

If necessary, the ophthalmologist can use a number of more complex techniques, such as visual field testing, macular sensitivity threshold testing, color vision testing, contrast sensitivity, FA and electrooculography.

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Toxic Crystalline Maculopathy

Tamoxifen

Tamoxifen (nolvodex, emblon, noltan, tamofen) is a selective estrogen receptor blocker used in some patients to treat breast carcinoma. Its few systemic and local (ocular) side effects are rare at daily doses of 20–40 mg. Retinal toxicity may occasionally develop in patients at higher doses and is characterized by the appearance, usually in the macula of both eyes, of relatively harmless, numerous, yellow, crystalline, ring-shaped deposits that persist even after treatment is stopped. Other, less common ocular side effects include infundibular keratopathy and optic neuritis, which are reversible when treatment is stopped. Because maculopathy is so rare, routine screening is not warranted.

Thioridazine

Thioridazine (melleril) is used in the treatment of schizophrenia and other psychoses. The normal daily dose is 150-600 mg. At doses exceeding 800 mg per day, even several weeks may be enough to reduce visual acuity and disrupt tempo adaptation. Clinical signs of progressive retinal toxicity are:

• Salt and pepper pigmentation disorder involving the central and mid-periphery of the retina.
• Coarse plaque-like pigmentation and focal absence of retinal pigment epithelium and choriocapillaris.
• Diffuse absence of retinal pigment epithelium and choriocapillaris.

Chlorpromazine

Chlorpromazine (largactil) is used as a sedative and in the treatment of schizophrenia. The daily dose is usually 75-300 mg. Retinal damage occurs with increasing daily doses over a long period and is characterized by the appearance of nonspecific pigment accumulation and granularity. Other benign ocular side effects include the deposition of yellow-brown granules on the anterior lens capsule and corneal endothelial deposits.

Canthaxanthin

This is a carotenoid used to improve sun tanning. Long-term use may result in bilateral formation of small, shiny, yellow deposits arranged symmetrically at the posterior pole in a "doughnut" pattern. The deposits are localized in the superficial layers of the retina and are harmless.

Methoxyflurane

Methoxyflurane (penlhrane) is a drug used for general inhalation anesthesia. It is metabolized by oxalic acid, which combines with calcium to form an insoluble salt (calcium oxalate) and is deposited in tissues, including the retinal pigment epithelium. Long-term use may lead to secondary hyperoxalosis, renal failure, and the deposition of harmless crystals in the retinal vessels.