Nitric Oxide Toxicity From Drug Use May Affect Macular Pathologic Changes

Repeated recreational use of volatile nitric oxide donor drugs can result in maculopathy.

Inhaling volatile nitric oxide donor drugs can result in poppers maculopathy — a condition accompanied by blurred vision, patchy central vision, metamorphopsia, photopsia, fluctuating vision, and altered color perception, according to a poster presented at the 2023 Southeastern Educational Congress of Optometry (SECO) meeting in Atlanta from March 1 to 5.

While frequently inhaled for their ability to create brief sensations of euphoria, sexual arousal, and myorelaxation, these drugs can also cause visual disturbances resulting from macular pathology of the outer retina. Despite a perception that poppers are not associated with any long-term sequelae, the poster presenters stress that repeated, long-term use can result in maculopathy.

Clinical evaluation using ophthalmoscopy and optical coherence tomography (OCT) may reveal a yellow lesion in the fovea and subfoveal outer retinal layer disruptions, respectively, among individuals with this disorder.

The poster presenters detailed 4 potential mechanisms of poppers maculopathy. The first states that poppers maculopathy may result from an upregulation of nitric oxide synthase — this activates guanylate cyclase and increases calcium current, resulting in calcium inhibition. A second mechanism suggests that nitric oxide increases photosensitivity, subsequently resulting in photic injury. The third proposes nitric oxide acts as a potent vasodilator and the change in ocular pressure causes injury. The final mechanism considers retinal damage secondary to microvascular toxicity in the choriocapillaris as a cause of poppers maculopathy.

The most effective way to diagnose poppers maculopathy is by use of spectral domain-OCT, according to the poster presenters, which will indicate a disruption or loss of the inner segment/ outer segment junction or ellipsoid zone. While there are currently no treatments for poppers maculopathy, research suggests that the condition may be partly reversible.


Lewandowska BI, Monelyon-Demeritt MJ. Pop the macula. Poster presented at: Southeastern Educational Congress of Optometry 2023 annual meeting; March 1 to 5, 2023; Atlanta, GA.