Nocturnal Hypoxia Linked to Wet Age-Related Macular Degeneration Risk

Robyn H. Guymer, MBBS, PhD

Credit: Centre for Eye Research Australia

Nocturnal hypoxia in obstructive sleep apnea (OSA) was associated with the risk of age-related macular degeneration (AMD), particularly its neovascular (wet) form (nAMD), according to new research.¹

Adjusting for relevant risk factors, including age, sex, smoking status, and body mass index (BMI), this multivariable analysis revealed a significant difference in the link between the oxygen desaturation index (ODI) and AMD severity. Those with moderate to severe OSA experienced a greater risk of nAMD.

“These findings may assist in providing much-needed additional strategies to mitigate the risk of developing the severe vision-threatening late form of nAMD,” wrote the investigative team, led by Robyn H. Guymer, MBBS, PhD, Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital.

Outer retina demands the largest oxygen supply per unit volume of any body tissue – any factor impacting this oxygen supply could put retinal health at risk.² OSA, the most common form of sleep-disordered breathing (SDB), is estimated to affect 1 billion worldwide, with most remaining undiagnosed. Age, obesity, and male gender are known as major risk factors linked to OSA.³

However, few studies have examined the link between OSA and ocular conditions, including AMD. In this study, Guymer and colleagues used in-the-home, overnight pulse oximetry, an objective measure of nocturnal hypoxia, to measure its association with AMD. The goal was to determine the relationship between nocturnal hypoxia and AMD severity and the high-risk sub-phenotype of reticular pseudodrusen (RPD).

Participants aged ≥50 years with AMD were recruited from natural history studies in Australia. Those in the control cohort had no apparent aging changes (lack of drusen) or normal aging changes (small drusen <63 µm). Exclusions were made based on any pre-existing ophthalmic condition associated with OSA or any retinal condition mimicking AMD.

A total of 225 participants were included in the final analysis, with 171 (76%) having AMD and 72 (42%) having coexistent RPD. Among those with AMD, more than half (53%) had early/intermediate AMD, 30% had geographic atrophy (GA), and 17% had nAMD.

All participants were given a wrist pulse oximeter to wear overnight for 3 consecutive nights to obtain nocturnal oxygen saturation measurements in the blood (SpO₂). The classification of OSA was defined based on the oxygen desaturation index (ODI) categorized as mild OSA with values of 5–15 or moderate-to-severe with values >15.

Upon analysis, Guymer and colleagues found no correlation between mild or moderate-to-severe OSA and an increased risk of AMD or AMD with RPD (P ≥.180). However, there was a significantly higher risk of AMD in the cohort based on a history of smoking (P = .004) and a greater risk of RPD was identified based on older age and female sex (P ≤.009).

In assessing AMD severity, the team observed significantly increased odds of late dry AMD or nAMD based on older age (P ≤.012) and any severity of AMD, based on a history of smoking (P ≤.037). Notably, moderate-to-severe OSA was associated with significantly higher odds of nAMD (P = .032), while mild OSA was not linked to differences in the likelihood of any AMD severity (P ≥.277).

Based on these data, Guymer and colleagues indicated nocturnal hypoxia could serve as an additional modifiable risk factor for AMD, particularly for nAMD, but further studies are needed to explore the relationship.

“Given the biological rationale for hypothesizing a potential relationship between nocturnal hypoxia and AMD, prior positive associations in the literature, the variability of ODI readings, and the large number of the elderly population with undiagnosed nocturnal hypoxia, larger studies, with formalized polysomnography would be beneficial to try to confirm or refute our findings,” they wrote.

References

1. _{Chaudhary A, Abbott CJ, Wu Z, et al. Nocturnal hypoxia and age-related macular degeneration. Clin Exp Ophthalmol. Published online August 1, 2024. doi:10.1111/ceo.14428}
2. _{Ramsey DJ, Arden GB. Hypoxia and Dark Adaptation in Diabetic Retinopathy: Interactions, Consequences, and Therapy. Curr Diab Rep. 2015;15(12):118. doi:10.1007/s11892-015-0686-2}
3. _{Benjafield AV, Ayas NT, Eastwood PR, et al. Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis. Lancet Respir Med. 2019;7(8):687-698. doi:10.1016/S2213-2600(19)30198-5}