A recent study explored the relationship between nocturnal hypoxia and AMD, particularly its late neovascular form. The findings suggest nocturnal hypoxia, as measured by oxygen desaturation index, may be a modifiable risk factor for neovascular AMD.

The investigators, in their Clinical & Experimental Ophthalmology article, highlighted a growing interest in understanding the role of outer retinal hypoxia in AMD. They noted that recent OCT-A studies have identified reduced blood flow and thinning of the choriocapillaris in AMD patients compared to age-matched healthy individuals, suggesting a connection with outer retinal hypoxia. The outer retina has the highest oxygen demand of any tissue in the body — particularly at night when photoreceptors are highly active to sustain energy-intensive processes like the dark current when photoreceptors are continuously depolarized and generating neurotransmitters. Thus, any disruption to this essential oxygen supply during nighttime could jeopardize retinal health.

To explore this connection further, a total of 225 participants aged 50 years and over were categorized into an AMD group and control group. The AMD group was further divided into early/intermediate AMD (53%), geographic atrophy (GA; 30%), and neovascular AMD (nAMD; 17%). Patients undergoing obstructive sleep apnea (OSA) treatment were excluded from the study.

Participants underwent home-based overnight pulse oximetry to measure oxygen desaturation index (ODI), defined as the number of oxygen desaturation events per hour. High-quality continuous recordings were obtained in 82% of participants over three nights. Multimodal imaging was then used to classify AMD and identify reticular pseudodrusen (RPD), a high-risk AMD sub-phenotype. 

Mild OSA had an ODI of 5 to 15 and was not significantly associated with AMD or its subtypes. Moderate-to-severe OSA with ODIs of 15 or more increased the odds of having nAMD but was not associated with early/intermediate AMD or GA. No significant association was found between moderate-to-severe OSA and the presence of RPD.

Smoking history was significantly associated with increased odds of all AMD severities, and older age was linked to late AMD, including nAMD, as well as GA. Higher ODI was associated with older age and higher BMI but not with sex or smoking history.

Hypoxia may exacerbate oxidative stress and inflammation in the retina, and contribute to AMD development, but “these findings may assist in providing much needed additional strategies to mitigate the risk of developing the severe vision threatening late form of nAMD,” the researchers concluded.

Because patients on OSA treatment were excluded, AMD and OSA cases may have been underrepresented. However, “larger studies, including longitudinal studies, as well as studies with formal polysomnography, would further explore this association of nocturnal hypoxia with AMD.” The researchers also noted that pulse oximetry offers a feasible and low-cost screening tool for nocturnal hypoxia in at-risk populations.