Systemic hypoxia, particularly anaemia-associated phenotypes, is associated with accelerated progression from non-proliferative to proliferative diabetic retinopathy and near-doubled legal blindness risk in a propensity-matched retrospective cohort study.
Systemic hypoxia was associated with a statistically significant increased risk of progression from NPDR to PDR.
The 5-year cumulative incidence of PDR was substantially higher in the systemic hypoxia cohort compared to controls.
Patients with systemic hypoxia had higher risks of multiple vision-threatening complications.
Anaemia was identified as the primary driver of PDR progression among the systemic hypoxia subgroups, while respiratory aetiologies were not independently associated after matching.
The study used the TriNetX Network database with a retrospective cohort design and propensity score matching to compare adults with NPDR with and without systemic hypoxia.
The authors propose that anaemia screening may represent an opportunity to reduce vision-threatening complications in diabetic patients.
This research suggests that people with diabetes who also have conditions causing low oxygen levels in the body — such as anaemia, sleep apnoea, or lung disease — are more likely to experience worsening of their diabetic eye disease. The study compared nearly 185,000 patients (about 92,000 with systemic hypoxia and 92,000 without) drawn from a large US healthcare database, carefully matching them so the groups were similar in other important characteristics. Patients with systemic hypoxia were about 24% more likely to develop proliferative diabetic retinopathy (the more severe, sight-threatening form of the disease) and faced roughly double the risk of becoming legally blind compared to those without these oxygen-depleting conditions. When the researchers looked more closely at which conditions were driving this risk, they found that anaemia (low red blood cell levels, which reduces the blood's ability to carry oxygen) was the main factor, rather than respiratory conditions like sleep apnoea or COPD. This suggests that the mechanism may involve insufficient oxygen delivery to the retina through the bloodstream rather than low oxygen in inhaled air alone. Patients with systemic hypoxia also more frequently needed intensive treatments such as laser therapy and eye surgery, indicating more advanced disease progression. This research suggests that screening diabetic patients for anaemia could potentially help identify those at higher risk of serious eye complications earlier, allowing for closer monitoring or earlier treatment. However, the authors emphasize that because this was a retrospective study using diagnostic codes rather than actual blood or oxygen measurements, the findings need to be confirmed in prospective studies before they should change clinical practice or screening guidelines.
Munir L, Yashar M, Kim K, Vaishnav A, Paulus Y. (2026). Role of systemic hypoxia in the progression of diabetic retinopathy: a propensity-matched retrospective cohort study.. BMJ open ophthalmology. https://doi.org/10.1136/bmjophth-2026-002941