Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in adults over 60. It damages the macula, the central part of the retina responsible for detailed sight, and can make it difficult to read, drive, or recognize faces. As populations age, AMD has become a growing public health concern.
Treatments for the advanced “wet” or neovascular form of AMD have improved greatly thanks to anti-VEGF injections, which block abnormal blood vessel growth in the retina. Yet, for the much more common early and intermediate “dry” forms, there are still no effective therapies to prevent or slow progression. These earlier stages are driven by chronic oxidative stress, vascular dysfunction, and low-grade inflammation, processes that unfold silently over many years. Finding a therapy that targets these mechanisms early could prevent vision loss before it becomes irreversible.
A fresh look at prostacyclin
Prostacyclin is a natural molecule produced by cells lining our blood vessels. It acts as a vasodilator, keeping vessels open, and as an inhibitor of platelet aggregation, preventing clot formation. Synthetic versions, known as prostacyclin analogues (PCA), include drugs such as iloprost, treprostinil, and epoprostenol. These medications are cornerstone therapies for pulmonary arterial hypertension (PAH), a condition marked by the narrowing of small lung arteries.
In the lungs, prostacyclin analogues do more than reduce pressure. They exert anti-inflammatory and protective effects, helping blood vessels remain stable and functional. They also enhance nitric oxide signaling, reduce oxidative stress, and improve survival in patients with PAH. This led to a question: if prostacyclin analogues protect the small blood vessels in the lungs, could they also protect those in the eye?
Shared mechanisms between lungs and eyes
At a biological level, the lungs and the eyes face similar challenges. Both depend on tiny, delicate capillaries that must stay open and healthy. Both are susceptible to injury from oxidative stress and chronic inflammation, which worsen with age.
In AMD, these same mechanisms lead to microvascular compromise, reduced oxygen delivery, and eventual degeneration of retinal tissue. If prostacyclin analogues can stabilize endothelial function and dampen inflammation elsewhere in the body, they might also help preserve retinal and choroidal health.
Using real-world data to test the idea
Traditionally, testing this hypothesis would require a lengthy and expensive clinical trial. Instead, we used TriNetX, a global federated health research network that securely aggregates de-identified medical data from millions of patients across hospitals and health systems.
TriNetX allows researchers to compare groups of patients, for example, those who took a particular drug versus those who did not, while ensuring the groups are otherwise similar. The platform uses a technique called propensity score matching to balance demographic and clinical characteristics, reducing bias and making the comparisons more reliable.
How the study worked
We identified patients aged 50 or older diagnosed with PAH. Some had received prostacyclin analogue therapy, while others had not. Using TriNetX, we divided them into two matched cohorts based on age, sex, race, cardiovascular and respiratory comorbidities, diabetes, and retinal conditions. Patients with a prior AMD diagnosis were excluded.
For those treated with prostacyclin analogues, the “index date” was the start of therapy; for untreated patients, it was the date of PAH diagnosis. From that point, we tracked new cases of both dry and wet AMD over time, spanning up to 15 years of follow-up.
TriNetX generated Kaplan-Meier survival curves and Cox proportional hazards models to compare AMD incidence between groups, providing time-to-event analysis while maintaining data privacy across institutions.
What we found
Across this large, multi-institutional dataset, patients who received prostacyclin analogues had a significantly lower risk of developing AMD over time compared with those who did not receive the drugs. This association remained consistent even after adjusting for other health factors. In short, people taking prostacyclin analogues for lung disease seemed to be less likely to develop age-related macular degeneration, an unexpected but biologically plausible finding.
Why it matters
The results suggest that prostacyclin signaling may have protective effects beyond the lungs, potentially helping to preserve the retina’s microvascular and immune balance. If confirmed, this could represent a novel systemic approach to AMD prevention, repurposing an existing, well-studied drug class. At present, no medication prevents or slows early AMD. A therapy that targets inflammation and microvascular health before irreversible retinal damage occurs could fill a major unmet need.
Strengths and limitations
The major strength of this approach is its real-world scale. TriNetX includes millions of patients from diverse backgrounds, enabling statistically powerful analyses that single-center studies cannot match. The platform also allows long-term, longitudinal tracking of health outcomes, treatment patterns, and disease trajectories.
However, real-world data come with limitations. Medical records may be incomplete or inconsistent, and diagnostic codes may not capture disease severity or subtle clinical details. While propensity score matching reduces bias, residual confounding may persist, since factors like lifestyle, nutrition, or genetics are not always recorded. Observational studies can reveal associations but cannot prove direct causation.
The next steps
These findings open new avenues for research. Laboratory studies could explore how prostacyclin analogues affect retinal cells, blood flow, and oxidative stress. Imaging-based observational studies might examine whether PCA users show fewer early signs of AMD on optical coherence tomography (OCT). Ultimately, prospective clinical trials would be needed to determine whether prostacyclin therapy can truly slow or prevent disease progression.
Beyond the specific results, this study showcases how large-scale health data platforms like TriNetX can accelerate discovery. By bridging fields as vascular biology, pulmonary medicine, and ophthalmology, researchers can uncover connections that might otherwise go unnoticed.
Conclusion
A drug developed to treat lung disease may also hold promise for protecting vision. By analyzing global, real-world data, our study found that prostacyclin analogue therapy was linked to a lower risk of developing age-related macular degeneration.
While more research is needed to confirm and explain this relationship, the findings highlight an exciting possibility: that existing vascular-protective drugs could be repurposed to safeguard the aging eye. They also illustrate how data-driven research can reveal unexpected links across disciplines, offering fresh hope for preventing vision loss in the world’s aging population.