Poppers maculopathy (PMP) is an emerging disease entity characterized by structural (foveal alteration) and functional (central vision) affection of the outer retinal architecture. “Poppers” in this case refers to drugs such as volatile alkyl nitrites that are commonly consumed by inhaling vapor. They’re often marketed with misleading labeling in small bottles similar to those of energy drink shots, implying that they’re meant to be consumed or inhaled.1 The FDA warns against purchasing or consuming them.

Three distinct phenotypes of PMP have been described in the literature, all with various outcomes. The disease’s underlying pathogenesis is still unknown. “Within the population who used poppers in 2015 in the United Kingdom (10% of the UK population), 2.2% reported a drug-related affection of visual function, with an additional 10% who described a possible effect of popper use on their eyesight,” explained the authors of a recently published paper on PMP.2

To learn more about PMP, they investigated a possible microvascular component on OCT-A, which they said is the “most adequate tool” for determining foveal and parafoveal changes in the microvasculature of PMP eyes in vivo. “While conventional fluorescein angiography and indocyanine green angiography are limited to two-dimensional analysis and do not allow for selective analysis of the choriocapillaris, OCT-A allows for three-dimensional analysis of flow signal of the parafoveal avascular arcade in form of superficial capillary plexus, deep capillary plexus and assessment of choriocapillaris within the foveal avascular zone,” they explained.

They included 12 patients with PMP (median age 40, all male) in their study and compared their health records, OCT and OCT-A data to a control group. The researchers performed an OCT-A evaluation of the retinal vascular plexus and choriocapillaris and determined PMP lesion type on OCT. Additionally, they assessed vessel density, vessel length density in the superficial and deep capillary plexus and flow deficits within the foveal avascular zone in the choriocapillaris.

They reported that 11 patients had ellipsoid zone-type lesions and one had a vitelliform-type lesion. Ultimately, they found no microvascular changes in PMP patients, observing no qualitative microvascular changes between the two groups and no differences in quantitative values for vessel density and vessel length density of the superficial and deep choriocapillaris. They also found no differences in flow deficits in the choriocapillaris in the two groups.

“Five patients discontinued the use of poppers between initial examination and follow-up visits,” the researchers noted in their paper. “Within these five patients, four showed a reestablished continuous ellipsoid zone upon follow-up (four of four with subfoveal disturbance of ellipsoid zone-type lesion).”

“PMP patients don’t show vascular anomalies in qualitative and quantitative analysis on OCT-A when compared with healthy controls,” they continued. “The constitution of the choriocapillaris within the foveal avascular zone, assessed as choriocapillaris flow deficit within the foveal avascular zone of PMP patients, didn’t show values outside of the range of the findings of healthy controls.”

“In PMP, the limits of homeostatic capacity of the foveal cone receptors appear to be breached,” they noted. They believe excessive oxidative stress to be one possible pathomechanism. The alkyl nitrites in poppers induce nitric oxygen upon oxidation, which causes an increase in cyclic guanosine monophosphate (cGMP). “cGMP is crucial in the photo-transduction pathway that enables calcium 2+ and sodium 2+ to permate cell membranes, which results in its depolarization,” they explained. “Nevertheless, continuous high levels of intracellular cGMP and Ca2+ cause oxidative stress, leading to photoreceptor cell death. Strikingly, in PMP patients, the retina apart from the subfoveal region appears to be remarkably normal.”

The researchers wrote that studying reactive oxygen species in PMP may point to antioxidants as possible prophylactic supplements in popper use or as a therapeutic agent. They concluded that, “Although structural improvement was observed in a significant number of our cases, function impairment remained in two cases, indicating persisting damage despite discontinuation of popper use. Taking into account the young median age of patients with PMP, awareness of possible long-term consequences of popper use should be increased. Further studies are warranted to histologically confirm our results.”

1. Nitrite “Poppers.” FDA.gov. https://www.fda.gov/consumers/consumer-updates/nitrite-poppers. Accessed December 3, 2021. Last Updated July 15, 2021.

2. Hamann T, Wiest MRJ, Brinkmann M, et al. Assessment of the microvasculature in poppers maculopathy. Graefes Arch Clin Exp Ophthalmol. November 21, 2021. [Epub ahead of print].