Poppers-associated retinal toxicity.
Catherine Vignal-Clermont, Isabelle Audo, José-Alain Sahel, Michel Paques
To cite this version:
Catherine Vignal-Clermont, Isabelle Audo, José-Alain Sahel, Michel Paques. Poppersassociated retinal toxicity.. The New England Journal of Medicine, 2010, 363 (16), pp.1583-5.
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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
fsacks@hsph.harvard.edu
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
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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
mp@cicoph.org
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
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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.
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Clostridium difficile — More Difficult Than Ever (October 30,
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