correspondence blood pressure is not reproducible enough to have clinical value. Optimal diets improve microvascular dysfunction, and they reduce blood pressure during the day and at night.2 Thus, diet is the treatment of choice for these linked disorders, and low sodium intake would have special effectiveness in such patients. We cannot agree with the opinion of de Oliveira and Santana to prescribe combination antihypertensive drug treatment for the primary prevention of cardiovascular disease in a patient with newly discovered essential hypertension. Such a patient could avoid drug treatment entirely if she optimizes her diet. Drug treatment for hypertension, although unquestionably effective in reducing cardiovascular events, has adverse effects that partially offset its benefits, as shown in a recent large trial.3 We agree with the statement by Oh and colleagues concerning sugars, and in our article we stated that “we encourage patients to eat . . . vegetables and fruit instead of snacks and desserts high in sugars, [and] fruit itself rather than juice.” We also recommended that “sections of the market that contain sweetened beverages, candies, and cookies should be avoided entirely” when shopping for food. We also agree that controlled trials are needed to determine direct effects that sugar and other carbohydrates have on blood pressure. We are completing such a trial using the controlled feeding methods of the DASH study (Effect of Amount and Type of Dietary Carbohydrates on Risk for Cardiovascular Heart Disease and Diabetes [OmniCarb]; ClinicalTrials.gov number, NCT00608049). Frank M. Sacks, M.D. Hannia Campos, Ph.D. Harvard School of Public Health Boston, MA [email protected] Since publication of their article, the authors report no further potential conflict of interest. 1. Reducing salt intake in populations: report of a WHO forum and technical meeting, 5-7 October 2006, Paris, France. Geneva: World Health Organization, 2007. 2. Uzu T, Kimura G, Yamauchi A, et al. Enhanced sodium sensitivity and disturbed circadian rhythm of blood pressure in essential hypertension. J Hypertens 2006;24:1627-32. 3. The ACCORD Study Group. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010; 362:1575-85. Poppers-Associated Retinal Toxicity To the Editor: “Poppers” (slang for various forms of alkyl nitrite) are volatile nitric oxide donors that have been used for decades as recreational drugs. Both the popularity of and legal tolerance for poppers have led to the perception that these drugs are relatively innocuous.1 Here, we describe four patients who were seen within a few months of one another and who had prolonged visual loss as a result of damage to foveal photoreceptors shortly after inhaling poppers. In January 2010, Patient 1, a 27-year-old woman, presented with an 11-day history of a reduction in bilateral vision and a “central bright dot” in both eyes. The night before the onset of symptoms, she had attended a party, at which both she and Patient 2 had inhaled poppers (brand name, Jungle Juice) and consumed approximately half a bottle of high-grade alcohol. Patient 1 was an occasional consumer of other brands of poppers but reported having had no previous visual symptoms. Her medical history was unremarkable. The visual acuity was 20/50 in the right eye and 20/40 in the left eye. Anterior segments and intraocular pressure were normal. The fundus examination showed a yellow foveal dot in both eyes (Fig. 1A and 1B, top row). Findings on highresolution optical coherence tomography were consistent with damage to the photoreceptor outer segment in the fovea of both eyes (Fig. 1A and 1B, bottom row). Color vision and full-field electroretinograms were normal. Isopropyl nitrite was identified by gas chromatography–mass spectrometry in the vapors from the popper vial. On follow-up examination 1 month later, the visual symptoms and ophthalmologic examination were unchanged. Within a 3-month period, we examined three other patients who also had visual loss with central phosphenes after inhaling isopropyl nitrite (see the Supplementary Appendix, available with the full text of this letter at NEJM.org). Two of these patients showed resolution of symptoms over several weeks. To our knowledge, over the past 10 years, there have been only two case reports of visual n engl j med 363;16 nejm.org october 14, 2010 The New England Journal of Medicine Downloaded from www.nejm.org on October 21, 2010. For personal use only. No other uses without permission. Copyright © 2010 Massachusetts Medical Society. All rights reserved. 1583 The n e w e ng l a n d j o u r na l A of m e dic i n e B Figure 1. Retinal Images of Patient 1 at Presentation 11 Days after Inhalation of Poppers. Shown are images of the patient’s right eye, with visual acuity of 20/50 (Panel A), and left eye, with visual acuity of 20/40 (Panel B). In the top row, fundus photographs show a bilateral yellow foveal dot (arrows). In the bottom row, optical coherence tomography shows altered reflectance of photoreceptor outer segments in the foveae (arrowheads). loss after inhalation of poppers,2,3 and the anatomical basis of this injury remains elusive. Thus, vision loss after intake of poppers is considered to be a rare event, although poppers-induced phosphenes are reported in Internet forums. The reason for the apparent outbreak of popper toxicity that we report here remains to be determined. It may have been due to an increased use of poppers in the population, to the availability of more powerful popper brands, or to improvements in retinal imaging technologies. Because the only compound we detected in the vapors from the vials was isopropyl nitrite, a very potent nitric oxide donor, it is likely that the visual symptoms were due to acute, massive release of nitric oxide. Nitric oxide modulates photoreceptor metabolism and function. It also activates guanylate cyclase,4 a key enzyme for recovery of photoreceptor function after phototransduction. However, guanylate cyclase activation is predicted to decrease light sensitivity, whereas the phosphenes reported by our patients suggest increased light sensitivity. Retinal damage was functionally and anatomically limited to the foveal center, a situation similar to that observed in photic injury. Experimentally, nitric oxide is indeed known to contribute to photic injury.5 However, our patients reported that they had not stared at bright lights. Because nitric oxide is a potent vasodilator, acute changes in ocular perfusion pressure might have contribut- 1584 n engl j med 363;16 ed to retinal damage, although photoreceptors are relatively resistant to short-term circulatory changes. Consumers and ophthalmologists should be aware of the possible retinal toxicity of poppers. In patients with recent bilateral visual loss and phosphenes, this diagnosis should be considered. Finally, the determination of the molecular basis for the toxic effects of poppers may be of interest to further document the role of nitric oxide in retinal function and diseases and to identify potential approaches to counter such toxicity. Catherine Vignal-Clermont, M.D. Fondation Ophtalmologique Adolphe de Rothschild Paris, France Isabelle Audo, M.D., Ph.D. José-Alain Sahel, M.D. Michel Paques, M.D., Ph.D. Quinze-Vingts Hospital Paris, France [email protected] Supported by the Institut National de la Santé et de la Recherche Médicale, the Direction de l’Hospitalisation et des Soins, and the Foundation Fighting Blindness. Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org. 1. Romanelli F, Smith KM, Thornton AC, Pomeroy C. Poppers: epidemiology and clinical management of inhaled nitrite abuse. Pharmacotherapy 2004;24:69-78. 2. Fledelius HC. Irreversible blindness after amyl nitrite inhalation. Acta Ophthalmol Scand 1999;77:719-21. 3. Pece A, Patelli F, Milani P, Pierro L. Transient visual loss nejm.org october 14, 2010 The New England Journal of Medicine Downloaded from www.nejm.org on October 21, 2010. For personal use only. No other uses without permission. Copyright © 2010 Massachusetts Medical Society. All rights reserved. notices after amyl isobutyl nitrite abuse. Semin Ophthalmol 2004;19: 105-6. 4. Goldstein IM, Ostwald P, Roth S. Nitric oxide: a review of its role in retinal function and disease. Vision Res 1996;36:2979-94. 5. Goureau O, Jeanny JC, Becquet F, Hartmann MP, Courtois Y. Protection against light-induced retinal degeneration by an inhibitor of NO synthase. Neuroreport 1993;13:233-6. Correspondence Copyright © 2010 Massachusetts Medical Society. instructions for letters to the editor Letters to the Editor are considered for publication, subject to editing and abridgment, provided they do not contain material that has been submitted or published elsewhere. 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In the last sentence of the Cerebral Perfusion and Orthostatic Intolerance subsection of Differential Diagnosis (page 1820), the parenthetical information should have read, “(miosis and anhidrosis),” rather than “(meiosis and anhidrosis).” The article has been corrected at NEJM.org. Clostridium difficile — More Difficult Than Ever (October 30, 2008;359:1932-40). In reference 25 (page 1939), the second author’s name should have been listed as “Gerson M,” rather than “Gerdsom M.” The article has been corrected at NEJM.org. notices Notices submitted for publication should contain a mailing address and telephone number of a contact person or department. We regret that we are unable to publish all notices re- ceived. Notices also appear on the Journal’s Web site (NEJM .org/medical-conference). The listings can be viewed in their entirety or filtered by specialty, location, or month. Erasme University Hospital The following meetings will be held in Brussels, unless otherwise indicated: “Doppler-Echocardiography in Intensive Care Medicine” (Nov. 16–18); “16th Postgraduate Refresher Course: Cardiovascular and Respiratory Physiology Applied to Intensive Care Medicine” (Nov. 30–Dec. 2); “Respiratory Monitoring” (Rome, Dec. 5–8); and “31st International Symposium on Intensive Care and Emergency Medicine” (March 22–25). Contact Erasme University Hospital, Université Libre de Bruxelles, Intensive Care Department, Route de Lennik 808, 1070 Brussels, Belgium; or call (32) 2 555 3631; or fax (32) 2 555 4555; or e-mail [email protected]; or see http://www .intensive.org. American Society of Tropical Medicine and Hygiene The following meetings will be held in Atlanta: “Certificate of Knowledge Examination” (Nov. 2) and “ASTMH 59th Annual Meeting” Nov. (3–7). Contact the American Society of Tropical Medicine and Hygiene, 111 Deer Lake Rd., Suite 100, Deerfield, IL 60015; or call (847) 480-9592; or fax (847) 480-9282; or e-mail info@astmh .org; or see http://www.astmh.org. International Scientific Conference on Gastro-Intestinal Microbial Ecology The conference will be held in Kosice, Slovakia, Nov. 9–11. Contact the Organizing Secretariat, PAMIDA International Ltd., Komenského 2656, 024 01 Kysucké Nové Mesto, Slovak Republic; or call (421) 918 707371; or fax (421) 41 4000123; or e-mail [email protected]; or see http://www .gutmicroecology.net. Abdominal Radiology Course 2011 The Annual Meeting and Postgraduate Course will be held in Carlsbad, CA, March 20–25. It is jointly presented by the Society of Gastrointestinal Radiologists and the Society of Uroradiology. Contact International Meeting Managers, 4550 Post Oak Place, Suite 342, Houston, TX 77027; or call (713) 965-0566; or fax (713) 960-0488; or see http://www.sgr.org or http://www .uroradiology.org. Harvard Medical School Center for Palliative Care The following course will be offered in Cambridge, MA: “Program in Palliative Care Education and Practice” (April 5–12, Nov. 2–8, 2011; deadline for submission of applications, Feb. 11). Contact HMS Center for Palliative Care, Dana–Farber Cancer Institute, 44 Binney St., SW530B, Boston, MA 02115; or call (617) 582-7859; or e-mail [email protected]; or see http:// www.hms.harvard.edu/pallcare/pcep.htm. Dallas-Leipzig International Valve 2010 The conference will be held in Dallas, Dec. 9–11. Contact Dallas-Leipzig International Valve, 7777 Forest Lane, Suite C-742, Dallas, TX 75230; or e-mail info@ dallasleipzigvalve.org; or see http://www.dallasleipzigvalve.org. Urgent Care Association of America The following meeting will be held: “2010 Urgent Care Fall Conference” (Phoenix, AZ, Oct. 22 and 23). Contact Lou Ellen Horwitz, Urgent Care Association of America, 4320 Winfield Rd., Suite 200, Warrenville, IL 60555; or call (877) 698-2262; or fax (630) 836-8518; or e-mail [email protected]. n engl j med 363;16 nejm.org october 14, 2010 The New England Journal of Medicine Downloaded from www.nejm.org on October 21, 2010. For personal use only. No other uses without permission. Copyright © 2010 Massachusetts Medical Society. All rights reserved. 1585