CRYSTALLINE RETINOPATHIES

Several chemicals can cause deposition of crystals in the retina. They include canthaxanthin, talc, and tamoxifen. In the majority of the cases, the patient is unaware of the presence of these crystals; they are found on a routine dilated retinal examination. Canthaxanthin has been used as an oral tanning agent, but its use seems to have diminished since the reports of deposits in the retina. Talc is typically seen in intravenous drug use, for which talc has been used as a filler in compounding the illegal drug. Tamoxifen is typically used in treating breast cancer. The number of cases with tamoxifen retinopathy has greatly declined since the daily dose was lowered to 10 to 20 mg per day.

Symptoms

Patients with either talc or canthaxanthin retinopathy are usually asymptomatic. However, talc retinopathy can be associated with arteriolar occlusions and retinal nonperfusion leading to neovascularization and even glaucoma. The original published reports of patients with tamoxifen retinopathy described mild decreases in central visual acuity.

Clinical Features

The crystals can be subtle or quite striking. Canthaxanthin can be overwhelming in the number of highly reflective crystals. Talc and tamoxifen crystals tend to be fewer and they are also less reflective.

The talc crystals can be more concentrated along the major retinal vessels. The crystals tend to be located in the inner, superficial layers of the retina. Tamoxifen retinopathy may be associated with lesions at the level of the retinal pigment epithelium as well.

Ancillary Testing

It is generally not necessary to perform additional testing in these patients. A thorough history will usually guide the clinician to the diagnosis. No pathognomonic findings are found on angiographic or electrophysiologic testing.

Pathology/Pathogenesis

Canthaxanthin retinopathy is usually associated with prolonged use. The crystals do decrease slightly after cessation of its use. Talc retinopathy is commonly associated with some cardiopulmonary shunt that allows the compound to enter the arterial circulation. Tamoxifen is a cationic amphophilic drug, and the deposits have been found in the nerve fiber and inner plexiform layers. The crystals are both intraand extracellular. Limited change is seen following discontinuation of the drug. Tamoxifen retinopathy is more likely to occur once the lifetime dose exceeds 90 g.

Treatment/Prognosis

The treatment of all the crystalline retinopathies is to stop the drug. In the case of tamoxifen, the dose could be lowered. The majority of affected patients

maintain good vision in spite of the presence of the crystals. Patients with talc retinopathy can develop further problems and therefore should be followed up and strongly encouraged to discontinue the use of illicit intravenous drugs.

Systemic Evaluation

No additional systemic evaluation is necessary if a history of medication or drug use is clear. Rare metabolic disorders such as primary hyperoxaluria may be associated with a crystalline retinopathy. Bietti’s crystalline retinopathy is a rare, inherited retinal disorder characterized by the presence of retinal crystals.

Canthaxanthin toxicity in a woman who used the drug for several months. Note the highly refractile yellowish crystals in the perifoveal region.

This fundus photograph reveals talc or magnesium silicate crystals in the right eye of a patient with a history of chronic intravenous drug abuse.

The fellow eye of the same patient reveals similar findings. The retinal crystals are located in the superficial layers of the retina.

Higher-magnification photograph of talc retinopathy. Note the perivascular location of the retinal crystals.

Large crystals in the right eye of a woman treated with unusually high doses of tamoxifen for several years. (Photograph reprinted with permission from Elsevier Science. [Gass JDM. Stereoscopic Atlas of Macular Diseases: Diagnosis and Treatment, 4th ed; 1997].)

The fellow eye of the same patient had similar findings. The crystals are larger than in the other crystalline retinopathies, and retinal pigment epithelial changes are also seen. (Photograph reprinted with permission from Elsevier Science. [Gass JDM. Stereoscopic Atlas of Macular Diseases: Diagnosis and Treatment, 4th ed; 1997].)

Several drugs may be associated with the development of cystoid macular edema (CME), including nicotinic acid (niacin), epinephrine, and latanoprost. The occurrence of CME with any of these agents is uncommon, and the causal relationship of latanoprost and CME has been questioned. Certain ocular factors may be associated with an increased risk of CME. In particular, epinephrine and latanoprost are more likely to be associated with CME in aphakic and pseudophakic eyes.

Symptoms

The usual symptoms associated with CME occur in patients with aphakia and pseudophakia. Meta-

morphopsia and reduced visual acuity may be found in the affected eye. These symptoms generally develop slowly over a period of weeks to months.

Clinical Features

Fundus examination reveals a cystic appearance of the fovea that is characteristic of CME. A yellowish or

orange discoloration of the fovea may occur as well. In general, no evidence of ocular inflammation is noted.

Ancillary Testing

Fluorescein angiography helps confirm the diagnosis of CME except in the case of nicotinic acid. With both epinephrine and latanoprost, the typical petaloid appearance of hyperfluorescence is seen in the late phase of the angiogram. Although nicotinic acid produces a classic cystic appearance of the fovea on funduscopic examination, no evidence of hyperfluorescence is observed with fluorescein angiography.

Pathology/Pathogenesis

Each of these agents may cause CME through a different mechanism. It is unknown how nicotinic acid produces CME. It appears to be related to the dose of nicotinic acid and typically occurs when the patient is taking more than 2 g of nicotinic acid per day. Latanoprost may have a prostaglandin-like effect on the retina that contributes to the development of CME.

Treatment/Prognosis

In each case, stopping or lowering the drug dosage is the proper treatment. Epinephrine-induced CME usually resolves after discontinuing the drug. Stopping nicotinic acid or lowering the dosage will clear the CME. The CME produced by latanoprost can be quite severe, and topical steroids or nonsteroidal agents may be necessary to help alleviate the CME. An alternative pressurelowering agent should be considered in patients with CME associated with latanoprost.

Systemic Evaluation

No systemic evaluation is necessary in patients with a history of exposure to nicotinic acid, epinephrine, or latanoprost. Other causes of CME should be excluded before CME is attributed to any of these medications.

Niacin toxicity demonstrates a marked cystic appearance of the macula in this patient who took 4 g of niacin per day for 18 months.

A distinguishing feature of nicotinic acid-related cystoid macular edema is the lack of hyperfluorescence on fluorescein angiography. This late-phase angiogram demonstrates normal macular hypofluorescence.

The fundus photograph of the left eye of the same patient reveals a similar cystic pattern in the fovea.

A late-phase angiogram of the left eye of the same patient is similar: the petaloid pattern of hyperfluorescence is absent.

This pseudophakic patient developed cystoid macular edema while taking latanoprost for ocular hypertension. Note the yellow foveal reflex.

Fluorescein angiogram of the same eye of the same patient demonstrates the classic petaloid pattern of hyperfluorescence observed in patients with cystoid macular edema.