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Association Between Melatonin Use and the Risk of Age-Related Macular Degeneration
TAKE-HOME MESSAGE
- In this study, the authors evaluated the potential associations between melatonin use and risks of age-related macular degeneration (AMD) incidence or progression. Overall, patients across various age groups (age groups, ≥50 years, ≥60 years, and ≥70 years) taking melatonin showed a lower risk of AMD incidence (RR, 0.42, 0.36, and 0.35) after matching cohorts for demographic and comorbidity variables. This association was also seen when including patients who were evaluated for AMD development 2 years after the initial analysis event. Additionally, patients taking melatonin had a reduced risk of progression to neovascular AMD compared with control groups, an association that also persisted across all age groups.
- Although further studies are needed, melatonin use may have benefits in reducing the risk of AMD incidence and progression.
abstract
This abstract is available on the publisher's site.
Access this abstract nowIMPORTANCE
Melatonin has been shown to oppose several processes that are known to mediate age-related macular degeneration (AMD), but whether melatonin can confer benefits against AMD remains unclear.
OBJECTIVE
To examine the association between melatonin supplementation and the risk of the development or progression of AMD.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study accessed data from TriNetX, a national database of deidentified electronic medical records from both inpatient and outpatient health care organizations across the US, between December 4, 2023, and March 19, 2024. Patients aged 50 years or older, 60 years or older, and 70 years or older with no history of AMD (AMD-naive group) and with a history of nonexudative AMD (nonexudative AMD group) were queried for instances of melatonin medication codes between November 14, 2008, and November 14, 2023. Patients were then classified into either a melatonin group or a control group based on the presence of medication codes for melatonin. Propensity score matching (PSM) was performed to match the cohorts based on demographic variables, comorbidities, and nonmelatonin hypnotic medication use.
EXPOSURE
The presence of at least 4 instances of melatonin records that each occurred at least 3 months apart.
MAIN OUTCOMES AND MEASURES
After PSM, the melatonin and the control cohorts were compared to evaluate the risk ratios (RRs) and the 95% CIs of having an outcome. For the AMD-naive group, the outcome was defined as a new diagnosis of any AMD, whereas for the nonexudative AMD group, the outcome was progression to exudative AMD.
RESULTS
Among 121 523 patients in the melatonin-naive group aged 50 years or older (4848 in the melatonin cohort [4580 after PSM; mean (SD) age, 68.24 (11.47) years; 2588 female (56.5%)] and 116 675 in the control cohort [4580 after PSM; mean (SD) age, 68.17 (10.63) years; 2681 female (58.5%)]), melatonin use was associated with a reduced risk of developing AMD (RR, 0.42; 95% CI, 0.28-0.62). Among 66 253 patients aged 50 years or older in the nonexudative AMD group (4350 in the melatonin cohort [4064 after PSM; mean (SD) age, 80.21 (8.78) years; 2482 female (61.1%)] and 61 903 in the control cohort [4064 patients after PSM; mean (SD) age, 80.31 (8.03) years; 2531 female (62.3%)]), melatonin was associated with a reduced risk of AMD progression to exudative AMD (RR, 0.44; 95% CI, 0.34-0.56). The results were consistent among subsets of individuals aged 60 years or older (AMD-naive cohort: RR, 0.36 [95% CI, 0.25-0.54]; nonexudative AMD cohort: RR, 0.38 [95% CI, 0.30-0.49]) and 70 years or older (AMD-naive cohort: RR, 0.35 [95% CI, 0.23-0.53]; nonexudative AMD cohort: RR, 0.40 [95% CI, 0.31-0.51]).
CONCLUSIONS AND RELEVANCE
Melatonin use was associated with a decreased risk of development and progression of AMD. Although lifestyle factors may have influenced this association, these findings provide a rationale for further research on the efficacy of using melatonin as a preventive therapy against AMD.
Additional Info
Disclosure statements are available on the authors' profiles:
Melatonin and Risk of Age-Related Macular Degeneration
JAMA Ophthalmol 2024 Jul 01;142(7)648-654, H Jeong, JK Shaia, JC Markle, KE Talcott, RP SinghFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Jeong and co-authors reported the results of a retrospective cohort study based on a large national database that evaluated the benefits of melatonin supplementation (MS) for preventing the development and progression of age-related macular degeneration (AMD). This is a well-designed study that included various categories of patients with no history of AMD or with nonexudative AMD. Patients were divided into subgroups based on their age. By using propensity score matching, each MS subgroup was matched with a non-treated subgroup (control).
The important finding of this study is that MS was associated with a decreased risk of AMD development (in the AMD-naïve subgroup) and progression (in the nonexudative AMD subgroup). These findings proved a working mechanism that melatonin possesses anti-inflammatory and antioxidant properties, which are supported by numerous in vitro and in vivo studies. However, according to the analysis of clinical data, it remains uncertain whether MS can be translated into clinical therapy for the prevention and treatment of nonexudative AMD, especially since the current dosing for MS, as documented in electronic medical records, is much lower than the experimental dosing reported in the literature. Therefore, a randomized controlled clinical trial evaluating MS with different dosing regimens in patients with AMD is required.