Letters to the Editor
Nilutamide is an androgen receptor blocker approved for treatment of prostate cancer. We report a patient treated with nilutamide who experienced impaired dark adaptation, a documented but seldom acknowledged side effect of the medication. The patient's symptoms were initially attributed to reduced ocular or visual cortex perfusion.
An 87-year-old man experienced several episodes of isolated painless bilateral loss of vision lasting from 10 to 15 minutes, always occurring as he moved from a bright environment to a darker one. The most prominent episode occurred upon entering a dimly lit restaurant after having been in direct sunlight. At first he could not see to read the menu. He reported no other symptoms. Over 15 minutes, his vision would gradually recover.
His medical history included two brainstem strokes years earlier without residual deficits, prostate cancer, and ventriculoperitoneal shunt placement for low-pressure hydrocephalus. He was pseudophakic in both eyes and had mild chronic open-angle glaucoma treated with dorzolamide hydrochloride. For several months, he had been using 150 mg nilutamide daily for prostate cancer, as well as niacin, clopidogrel, aspirin, and simvastatin.
The patient had previously been evaluated by an ophthalmologist and neuro-ophthalmologist. The visual episodes were initially interpreted as either transient ischemic attacks of the posterior circulation or light-induced amaurosis.
The patient was referred for a second neuro-ophthalmologic consultation. Best-corrected visual acuity was 20/25 in both eyes. Humphrey 24-2 visual field examination showed nasal depression in the right eye and a slight inferior arcuate scotoma in the left eye, consistent with his history of glaucoma. The pupils were equal, and there was no afferent pupil defect. Results of slit lamp examination were normal with well-positioned posterior chamber intraocular lenses. Tensions by applanation tonometry were 17 mm Hg right eye and 19 mm Hg left eye. Gonioscopy was grade IV bilaterally. His cup-to-disk ratio was 0.4 right eye and 0.45 left eye, consistent with visual field loss. Findings from the fundus examination was otherwise normal. Complete blood count, erythrocyte sedimentation rate, and C-reactive protein showed normal values, and findings from carotid ultrasound and echocardiography were normal. MRI of the brain with gadolinium was unchanged.
The patient discontinued use of nilutamide. His visual symptoms resolved completely within several weeks.
Delayed dark adaptation caused by nilutamide has a prevalence ranging from 12.9 to 90% when patients are using a daily dose of 300 mg (1-8); this side effect is dose dependent (2,9). Nilutamide acts as an androgen inhibitor through receptor binding and is approved by the Food and Drug Administration (FDA) for treatment of metastatic prostate cancer in combination with surgical castration. To date, it is the only reported compound in its class to cause these visual symptoms and is not considered to offer any advantage in efficacy over other antiandrogens (10). To our knowledge, there has been only one published report quantifying this delayed dark adaptation effect via photostress recovery time (PSRT) (1). In that study, PSRT increased to an average of 9 minutes, with normal recovery time being 1-2 minutes. In other reported cases, patients have reported painless bilateral visual impairment upon transition into a darker area, particularly on entering a building on a bright day. The latency between first use of the medication and symptom onset has not been well documented.
Patrick Chan, BA
Jeffrey G. Odel, MD
Department of Ophthalmology, Columbia University College of Physicians and Surgeons, New York, New York, firstname.lastname@example.org
1. Harnois C, Malenfant M, Dupont A, et al. Ocular toxicity of Anandron in patients treated for prostatic cancer. Br J Ophthalmol
2. Brisset JM, Boccon-Gibod L, Botto H, et al. Anandron (RU 23908) associated to surgical castration in previously untreated stage D prostate cancer: multicenter comparative study of two doses of the drug and of a placebo. Prog Clin Biol Res
3. Janknegt RA, Abbou CC, Bartoletti R, et al. Orchiectomy and nilutamide or placebo as treatment of metastatic prostatic cancer in a multinational double-blind randomized trial. J Urol
4. Namer M, Toubol J, Caty A, et al. A randomized double-blind study evaluating Anandron associated with orchiectomy in stage D prostate cancer. J Steroid Biochem Mol Biol
5. Beland G, Elhilali M, Fradet Y, et al. A controlled trial of castration with and without nilutamide in metastatic prostatic carcinoma. Cancer
6. Navratil H. Double-blind study of Anandron versus placebo in stage D2 prostate cancer patients receiving buserelin: results on 49 cases from a multicentre study. Prog Clin Biol Res
7. Decensi AU, Boccardo F, Guarneri D, et al. Monotherapy with nilutamide, a pure nonsteroidal antiandrogen, in untreated patients with metastatic carcinoma of the prostate. J Urol
9. Du Plessis DJ. Castration plus nilutamide vs castration plus placebo in advanced prostate cancer: a review. Urology
10. Dole EJ, Holdsworth MT. Nilutamide: an antiandrogen for the treatment of prostate cancer. Ann Pharmacother