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Obstructive sleep apnea (OSA) was linked to a more than twofold risk of developing age-related macular degeneration (AMD) in a retrospective cohort study.

Among 58,700 matched pairs of patients with OSA and controls, a 5-year analysis found that the OSA group was more likely to develop nonexudative AMD (2.05% vs 0.76%; HR 2.64, 95% CI 2.37-2.96, P<0.001) and exudative AMD (0.53% vs 0.23%; HR 2.48, 95% CI 1.99-3.11, P=0.002).

The patients with OSA were also more likely to require anti-VEGF injections to treat AMD (HR 2.85, 95% CI 2.26-3.59, P<0.001), reported Ehsan Rahimy, MD, of Byers Eye Institute and Palo Alto Medical Foundation in California, and colleagues in .

Patients with preexisting AMD who developed OSA also had a higher potential risk of worsening disease via the development of geographic atrophy or wet/exudative AMD.

While there had been some "scattered evidence" linking OSA and AMD previously, said co-author Ahmed M. Alshaikhsalama, BS, of UT Southwestern Medical Center in Dallas, "we aimed to reexamine this potential association in a large U.S. population and look at the potential for preexisting AMD to become worse."

The magnitude of the excess risk of AMD in the patients with OSA came as a surprise, he told 番茄社区app.

A prior linked OSA to only a 1.36-fold increase in AMD risk and found no significant link to progression from nonexudative to exudative AMD. Cecilia S. Lee, MD, of the University of Washington in Seattle and an author on that earlier study, agreed that the magnitudes of risk associated with geographic atrophy (HR 7.00) and exudative AMD (HR 2.87) were "somewhat surprising."

The new study was "well-conducted," Lee told 番茄社区app. She suggested that the differences in findings might have been due to different population demographics, data collection methods, and analytic approaches.

Potential Mechanisms

Overall, the findings "make us wonder how local fluctuations in oxygen levels may impact the course of AMD and ask what might be happening at the cellular level that contributes to disease development," Alshaikhsalama said.

According to him, "one theory is that the intermittent nighttime hypoxia caused by OSA leads to oxidative stress and inflammation, which can damage the retina and contribute to AMD. There's also evidence that OSA is linked to thinner choroids -- similar to what we see in AMD -- which might reduce blood flow to the outer retina."

Alshaikhsalama added that "the repeated airway obstructions in OSA can cause microvascular damage, which could make things worse for the retina."

However, he cautioned that the study doesn't prove that OSA causes AMD. "We still don't know if OSA is the sole factor behind this association or if there is a genetic predisposition or another health factor that our study and others might have missed. We also don't know if treatment with CPAP [continuous positive airway pressure] or bilevel ventilation would resolve or reverse its potential effect on AMD. More studies are required to investigate all these questions."

Alshaikhsalama noted that all the patients with OSA in the study had been diagnosed and were prescribed treatment. However, OSA therapy "has notoriously poor adherence rates."

Study Details

For the study, researchers tracked health data from the TriNetX platform for people with age-related cataracts from 2004 to 2024. This allowed researchers to ensure that subjects all had undergone a comprehensive eye exam.

After propensity score matching, the characteristics of the 58,700 subjects in the OSA cohort were: 49% male, 66% white and 18% Black, 53% with diabetes mellitus, 71% overweight or obese, and 86% with hypertension. The 58,700 subjects in the control group had nearly identical demographics.

At 5 years, the researchers found no significant link between OSA and macular hemorrhage (0.67% vs 0.58%; HR 1.05, 95% CI 0.90-1.21, P=0.98) or legal blindness (0.22% vs 0.23%; HR 1.00, 95% CI 0.78-1.29, P=0.68). "The lack of significant association between OSA and macular hemorrhage or legal blindness is somewhat unexpected, as these complications often accompany advanced AMD," Lee said.

In matched groups of 4,705 subjects with non-advanced AMD, those in the OSA group had a higher rate of geographic atrophy (3.15% vs 0.32%; HR 7.00, 95% CI 4.47-11.0, P=0.03) and exudative AMD (8.50% vs 3.00%; HR 2.87, 95% CI 2.37-3.48, P=0.03).

The authors noted limitations such as the reliance on coding and on subjects who had age-related cataracts. The study also didn't take cigarette smoking, a risk factor for AMD, into account. Nor did it track use of , which are used to slow AMD progression.

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