Drug-Induced Maculopathy

Mahmood J. Khan; Thanos Papakostas; Kyle Kovacs; Mrinali P. Gupta


Curr Opin Ophthalmol. 2020;31(6):563-571. 

In This Article

Crystalline Maculopathies


Canthaxanthin is a naturally occurring chemical that is commonly utilized in food colorings, dyes, and skin tanning agents. Fundus findings demonstrate birefringent, yellow and red crystals most concentrated in the ciliary body and the macula, often in an annular configuration. Even in the setting of retinopathy, most patients have usually been noted to have normal vision.[29] Diagnostic workup with OCT localizes the crystals to the outer plexiform layer.[2] Discontinuation may promote gradual clearing of the deposits, which may coincide with detection of high plasma levels of canthaxanthine.[2]


Methoxyflurane is an inhalational anesthetic that is metabolized to oxalic acid, which in turn combines with serum calcium to form an insoluble calcium oxalate salt. Fundus findings include crystal deposits in the posterior pole along arterioles, which appear as yellow-white crystalline deposits similar to those found in 'flecked retina' disorders. The agent should be discontinued, although the crystalline retinopathy is irreversible.


Talc is a hydrated magnesium silicate that is routinely used as an inert filler in oral medications such as methylphenidate hydrochloride (Ritalin) or methadone. When these oral medications are injected intravenously in cases of drug abuse, the talc particles embolize to the lungs and with time can eventually enter the systemic circulation, leading to retinal vascular occlusion.[30] Typically, crystalline deposits are noted along the arterioles in the posterior pole. In the acute phase, associated retinal hemorrhages and cotton wool spots may be noted. There is no treatment for the posterior pole findings. Rarely, peripheral retinal avascularity may be noted with peripheral, that is capillary nonperfusion, cotton wool spots, microaneurysms, and in later stages, retinal neovascularization and its sequelae.[31] Neovascular complications are treated with laser photocoagulation for neovascularization and vitrectomy for nonclearing vitreous hemorrhages.


Tamoxifen is a nonsteroidal estrogen antagonist used for the treatment of early and advanced estrogen receptor positive and negative breast cancer.[32] Ocular complications are rare with tamoxifen therapy but can include cataracts, vortex keratopathy, optic neuritis, and retinopathy. The retinal findings of tamoxifen retinopathy have been described as cystoid changes or outer retinal defects which, both of which are well identified through OCT, and the presence of[33] refractile, yellow crystals at the level of the nerve fiber layer (NFL) and IPL that may begin as a perifoveal ring.[34] ERG may demonstrate decreased photopic and scotopic a-wave and b-wave amplitude.[35] Discontinuing the medication can resolve the crystals and associated cystoid changes, but the outer retinal defects persist.