Using “poppers,” which are volatile alkyl nitrite compounds inhaled for their sexual enhancement and psychoactive effects, can be associated with maculopathy, according to a new case series from the UK.

"This was a small study of 12 cases, but it adds to previous reports of poppers maculopathy, and we suspect there may be many more unidentified clinical and subclinical cases in areas where poppers use is prevalent,” Dr. Rebecca Rewbury from Sussex Eye Hospital, Brighton and Sussex University Hospitals Trust, in Brighton, told Reuters Health by email.

In the UK, poppers rank fourth among popular recreational drugs after cannabis, cocaine and ecstasy. Maculopathy emerged as a serious side effect of poppers use after isopropyl nitrite replaced isobutyl nitrite as an ingredient following legislative changes that classified the latter as a class II carcinogen. Dr. Rewbury and colleagues present 12 cases of visual disturbance, all in men, associated with poppers use in their report, online April 10 in the British Journal of Ophthalmology. Impaired central vision (blurriness or scotoma) occurring within hours or days of inhalation was the most frequently reported ocular symptom.

Fundoscopy revealed subtle yellow–colored foveal deposits, and spectral domain optical coherence tomography revealed disruption of the inner segment/outer segment junction in the subfoveal region in all cases. Anterior segments and intraocular pressures were normal in all cases.

Six of the products analyzed by nuclear magnetic resonance spectroscopy contained approximate 50:50 mixtures of isopropyl nitrite and isopropyl alcohol. Two samples of products branded Jungle Juice Plus had different ingredients: one contained a mixture of compounds tentatively identified as having amyl, 2–methyl butyl and isobutyl structure; the other contained a mixture of amyl nitrate, 2–methyl butyl nitrite and the corresponding alcohols. In three of these 12 cases, patients had used poppers for 20 years or more, only noticing symptoms on switching to a new brand.

In general, symptoms and imaging abnormalities improved over time. Six individuals abstained from poppers years after diagnosis and most were asymptomatic within a few months, with improvements in measured visual acuity.

One individual who had used poppers regularly for years, however, showed no improvement 3 months after cessation. Outcomes with continued poppers use were variable, with some individual showing improvement after switching to a different brand and others showing improvement with continued use of the same brand.

"The pathological mechanism of popper toxicity remains to be determined, and there is no obvious reason why isopropyl nitrate should be more toxic than isobutyl nitrate," the researchers note.

“People who use poppers should be aware that they can cause damage to the fovea – the central part of the retina used for detailed vision, which is important for activities such as reading and using computers,” Dr. Rewbury said.

“We would hope that physicians would consider it as a diagnosis and specifically ask about poppers use. It will also be important to monitor cases of poppers maculopathy, especially in chronic users of isopropyl nitrite, as the longer–term effects are unknown,” she said.

“We can’t predict who will be affected and it is unclear why some people develop retinal damage after using poppers only once,” Dr. Rewbury added. “There is no treatment, but reassuringly, the condition appears to be mostly reversible if patients stop using poppers.”

— Will Boggs, MD