Ocular growth is regulated by a vision-dependent cascade that begins in the retina and communicates signals to the RPE, choroid and then the sclera, where tissue biomechanics produce axial elongation changes to reduce or eliminate refractive errors. Studies suggest that behavioral and environmental factors can influence the way this cascade functions, and they may be responsible for common refractive errors such as myopia in children.

Because an adenosine receptor (ADOR) antagonist called 7-MX is known to reduce form-deprivation and lens-induced myopia in mammalian animal models when taken orally, a recent study investigated whether topically instilled caffeine, another non-selective ADOR antagonist, slows the progression of myopia (vision-induced axial elongation) in monkeys. The results suggest that ADOR antagonists may be potential treatments for preventing or slowing myopia progression.

The study included 14 baby rhesus monkeys who received a 1.4% caffeine solution instilled in both eyes, twice each day, beginning at 24 days of age until 135 days of age. While on this caffeine dose, the monkeys were also fitted with helmets that had either -3D (n=8) or +3D (n=6) spectacle lenses positioned in front of lens-treated eyes and zero-powered lenses in front of fellow control eyes. The researchers obtained control data from eight vehicle-treated animals raised with monocular -3D spectacles. They also had access to historical comparison data from otherwise untreated lens-reared controls and 41 normal monkeys.

The researchers reported that the vehicle controls and untreated lens-reared controls “consistently developed compensating axial anisometropias.” They also found that the caffeine regimen promoted hyperopic shifts in both lens-treated and fellow control eyes. A total of 26 of the 28 caffeine-treated eyes became more hyperopic than the median normal monkey, the researchers noted.

Topical caffeine produced qualitatively similar effects on refractive development as oral 7-MX, which led the researchers to conclude that ADOR antagonists may be useful strategies for combating myopia development in children.

Smith EL, Hung LF, She Z, et al. Topically instilled caffeine selectively alters emmetropizing responses in infant rhesus monkeys. Exp Eye Res. 2021;203:108438.