Age-related macular degeneration (AMD) remains one of the leading causes of vision loss among older adults
While treatments such as anti-vascular endothelial growth factor (VEGF) injections have transformed outcomes for many patients with wet AMD, there is still no cure for the disease— making prevention and risk reduction areas of ongoing interest
I’m listening …
One reason researchers continue exploring new approaches: inflammation
Over the years, evidence has increasingly suggested that inflammatory processes play an important role in AMD development, leading some investigators to wonder whether anti-inflammatory medications might influence future disease risk
As such: A recent study published inOphthalmologyexplored that possibility using data from more than 1.2 million patients
The findings suggest that individuals prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) may be less likely to develop AMD than those who never received NSAID prescriptions
Why would anti-inflammatory drugs affect AMD in the first place?
Part of the reasoning comes from what researchers currently understand about AMD biology
AMD is no longer viewed solely as a disease of aging. Chronic inflammation is believed to contribute to both nonexudative and exudative forms of the condition, influencing processes such as retinal pigment epithelium dysfunction, drusen formation, and abnormal blood vessel growth
And because NSAIDs work by inhibiting cyclooxygenase (COX) enzymes involved in inflammatory signaling, researchers have questioned whether those medications could potentially influence AMD development as well
This isn’t necessarily a new idea though, right?
Right. Previous studies have already explored possible links between NSAID use and AMD risk—but results have been mixed
Differences in study design, patient populations, and sample sizes have made it difficult to determine whether a true association exists
So to help answer that question, the authors of the current study analyzed one of the largest datasets examined to date
And how did researchers study this connection?
They conducted a retrospective cohort study using the TriNetX electronic health records (EHR) database
The investigators identified patients who received NSAID prescriptions between 2015 and 2024 and compared them with individuals who had no history of NSAID use
To make the comparison as balanced as possible, the two groups were matched based on factors including:
- Age
- Sex
- Race
- Smoking status
- Common medical conditions associated with AMD risk
The primary goal was straightforward: determine whether patients prescribed NSAIDs developed AMD at different rates than patients who were never prescribed those medications
Who ended up being included?
The final study population was substantial, with the following included:
- 634,794 patients prescribed NSAIDs
- 634,794 patients without NSAID prescriptions
The average age was approximately 60 years in both groups, while the analysis itself also accounted for numerous conditions that could potentially influence AMD risk: hypertension, diabetes, cardiovascular disease, obesity, smoking history, cerebrovascular disease, and rheumatoid arthritis
So what did they find?
The results pointed in the same direction throughout the study
Compared with patients who were not prescribed NSAIDs, those who received NSAID prescriptions demonstrated a lower risk of developing AMD at every measured follow-up interval
Researchers observed reduced risk at:
- 6 months (hazard ratio [HR] 0.31)
- 1 year (HR 0.36)
- 3 years (HR 0.42)
- 5 years (HR 0.48)
Go on …
Across the entire study period, NSAID users demonstrated an HR of 0.58 compared with non-users. The association was also observed in both major AMD categories
Compared with non-users, NSAID users demonstrated lower risk of:
- Nonexudative AMD (HR 0.56)
- Exudative AMD (HR 0.62)
Taken together, the findings suggest a consistent association between NSAID use and lower future AMD risk
Were certain NSAIDs associated with a bigger effect?
The researchers also looked at specific medication categories (though the study did not specify how long patients remained on their respective NSAID therapies)
Patients prescribed aspirin demonstrated a lower AMD risk than non-users, with an HR of 0.72
An even stronger association was observed among patients prescribed non-selective COX inhibitors (i.e. Ibuprofen Naproxen), who demonstrated a hazard ratio of 0.41
Interestingly, the relationship persisted across a wide range of patient groups
And when factoring in those aforementioned conditions?
NSAID users with those conditions all demonstrated lower AMD risk compared with similar patients who were not prescribed NSAIDs
The authors’ input on this: It’s difficult to know exactly why
- One possibility is that inflammatory pathways associated with these comorbidities may also influence AMD development—potentially making inflammation-modifying therapies more relevant in those populations.
Are there any important limitations?
Yes. The biggest limitation: this was an observational study
While the findings demonstrate an association between NSAID use and lower AMD risk, they cannot prove that NSAIDs directly prevented AMD from developing
Other limitations to consider:
- Researchers could not verify whether patients actually took the medications they were prescribed.
- Prescription records indicate that a medication was prescribed, but not necessarily that it was taken consistently.
- Residual confounding remains confounding, as—even with extensive matching—patients prescribed NSAIDs may differ from non-users in ways that are difficult to fully capture through EHRs alone.
The authors also pointed out that patients with multiple medical conditions often interact with healthcare systems more frequently, which could influence both medication documentation and disease detection
How are the authors interpreting these findings?
The authors were careful not to overstate what the data show
Rather than claiming NSAIDs prevent AMD, they described the findings as evidence of a possible protective association that warrants further investigation
From a biological standpoint: The results fit with existing theories regarding the role of inflammation in AMD pathogenesis
- If inflammation contributes meaningfully to disease development, it is plausible that medications targeting inflammatory pathways could influence risk.
At the same time, they emphasized that additional research will be necessary before any clinical recommendations can be made
So what could this mean going forward?
One interesting aspect of the study is that the association was observed across both dry and wet AMD
That consistency may provide additional support for the idea that inflammation contributes to multiple stages of AMD development rather than a single disease subtype
That said, these findings should not be interpreted as a reason for patients to begin taking NSAIDs specifically to prevent AMD. Long-term NSAID use carries its own potential risks, and this study was not designed to evaluate treatment recommendations
Anything else?
What the findings do provide is another piece of evidence supporting inflammation as an important area of AMD research
As such: Future studies will be needed to determine whether the relationship is truly causal and whether specific anti-inflammatory strategies could eventually play a role in prevention
