Long-Term NSAID Use May Be Protective in AMD

Bobeck S. Modjtahedi, MD

A study examining the relationship between nonsteroidal anti-inflammatory (NSAID) use and age-related macular degeneration (AMD) has determined that long-term use of NSAID is associated with lower risk of exudative, commonly referred to as wet, AMD (wAMD).

Lead author Bobeck S. Modjtahedi, MD, with the Department of Ophthalmology and Eye Monitoring Center at Kaiser Permanente Baldwin Park Medical Center in California, and colleagues in the Kaiser Permanente System, stated that although their study determined that the “overall impact of NSAIDS on AMD is small,” the reduced risk of wAMD associated with long-term NSAID users “may point to a protective effect and deserves further study as a possible mechanism to modulate disease risk.”

The prospective cohort study on NSAID and AMD included 51,371 participants in the California Men's Health Study (CMHS) conducted by Kaiser Permanente. Of the total participants, 292 were diagnosed with wAMD and 1536 with non-exudative, or dry, AMD. The CMHS included men between the ages of 45 and 69 years old.

Participants were asked to complete a baseline questionnaire in 2002—2003 which included sociodemographic data, personal and family health history, health conditions, medication use, tobacco and alcohol use, and healthcare utilization, and received a follow-up survey in 2006 (mean time to follow-up, 7.4 years). Information on AMD diagnosis post-initial survey was retrieved via electronic medical records in the Kaiser Permanente system. Patients reporting AMD as diagnosed health condition in the baseline questionnaire were excluded from the study.

Modjtahedi and colleagues characterized participants as NSAID users based on long- and short-term use indications on the survey. The total number of NSAID users among the study population was 16.4% (n = 8431) short-term users, 20.5% (n = 10,554) long-term users, and 13.6% (n = 7012) former users. The researchers also collected data on long- and short-term aspirin users, specifically finding that among the study population, 13.6% (n = 6997) were short-term, 14.3% (n = 7352) were long-term users, and 7.9% (n = 4057) were former users.

The data from the initial 2002-2003 baseline survey showed that 1.8% of study NSAID and aspirin only users were diagnosed with dry AMD in comparison to 1.7% non- aspirin/NSAID users. The 2002-2003 baseline survey also showed that 0.21% of any NSAID users and 0.24% of aspirin users were diagnosed with wAMD in comparison to 0.19% of non- aspirin/NSAID users.

Modjtahedi and colleagues reported that during the follow-up period, 0.06% (n = 292) of men were diagnosed with wAMD and 3% (n = 1536) were diagnosed with dry AMD.

Results of the study showed that after factoring for an increased risk of wet and dry AMD due to race and age and smoking, that the risk of wAMD was “statistically significantly lower in patients with longer-term use of any NSAIDS” (hazard ratio [HR], 0.69; 95% CI, 0.50—0.96; P = .029), but that there was no statistically significant difference between patients with long-term non-aspirin NSAIDS (HR, 0.53; 95% CI, 0.25—1.13; P = .10) and patients with long-term aspirin use (HR, 0.79; 95% CI, 0.53—1.07; P = .12).

The researchers also found no significant association between wAMD and other (short-term/former use) NSAID use categories. Modjtahedi and colleagues also reported that new users of any NSAIDs (HR, 0.79; 95% CI, 0.68—0.93; P = .0039) and aspirin (HR, 0.82; 95% CI, 0.70—0.97; P = .018) had a lower risk of dry AMD, although this decreased risk was not evident in non-aspirin NSAID users (HR, 0.89%; 95% CI, 0.72—1.10; P = .28).

“The possible relationship between NSAID use and AMD is an area of considerable interest, given the pervasive use of NSAIDs and the significant disease burden of AMD,” Modjtehedi wrote. He theorized that NSAIDS may play a protective role in AMD development associated with inflammation in AMD pathogenesis.

Although Modjtehedi and colleagues stated that it is too early to determine whether the use of NSAIDs—particularly longer-term use of NSAIDS—could be a means to delay or protect against AMD development, or to determine the exact relationship between reduced risk of wet AMD and longer-term NSAID use, the study results represent “a new avenue for future investigations into whether the risk of exudative [wet] AMD can be therapeutically mitigated” with the use of NSAIDs.

Modjtehedi pointed out that there have been several studies on the relationship between aspirin and AMD producing mixed results, perhaps due to the “complex and intertwined pathologic mechanisms [of AMD], which make elucidating the influence of individual factors such as NSAID use challenging,” and that “the effect of NSAIDs on oxidative stress and production of reactive oxygen species," both important factors in AMD, are currently unclear.

Since the data showed that the possible protective relationship between NSAID use and AMD was only statistically significant in longer-term NSAID users, the researchers believe that lowered risk of AMD may be dependent on the duration of exposure, but further research is needed to determine whether long-term NSAID use can be harnessed in a clinically meaningful way to modify risk.

The study, “The Relationship Between Nonsteroidal Anti-inflammatory Drug Use and Age-related Macular Degeneration,” was published in the American Journal of Ophthalmology.

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