A large-scale, retrospective evaluation found that patients with a history of melatonin use were nearly half as likely to develop AMD or progress to exudative AMD as patients who did not take the supplement, though clinical studies are needed to further investigate this potential protective effect.
Study Design
This retrospective cohort study used data from the TriNetX database to assess the relationship between melatonin use and the development of AMD, including the risk of progression to exudative AMD. Based on demographic variables, comorbidities, and non-melatonin hypnotic medication use, patients were propensity score–matched into a melatonin group and a control group (4580 individuals each). Melatonin use was defined as having at least 4 code-documented instances of melatonin supplementation, each occurring at least 3 months apart.
Outcomes
Overall, patients in the melatonin use group had a lower risk of developing AMD than patients who were not using melatonin (relative risk [RR]: 0.42). A subanalysis of 4064 patients ≥50 years of age in the melatonin group who had AMD found that these patients had a lower risk of progressing to exudative AMD than matched patients who were not using melatonin (RR: 0.44). Similar trends were seen in analyses of patients ≥60 years of age and ≥70 years of age.
Limitations
The study is impacted by the inherent limitations of using large databases, including the inability to assess the impact of certain potential confounders (e.g., Age-Related Eye Disease Study formula multivitamins) or modifiable AMD risk factors (e.g., diet). The duration of use and dose of melatonin was not standardized.
Clinical Significance
This study provides further support for clinical trials investigating the role of melatonin supplementation in preventing or minimizing the development of AMD or exudative AMD progression. The current data is not sufficient to support the recommendation of melatonin to prevent AMD, so it will not change my clinical practice, but I look forward to further research on melatonin and its effects on AMD.
Financial Disclosures: Dr. Ajay Kuriyan discloses financial relationships with 4DMT, Adverum, Annexon, National Eye Institute, Novartis, Alcon Pharmaceuticals (Grant Support); Alimera Sciences, Allergan, Bausch + Lomb, EyePoint Pharmaceuticals (Consultant/Advisor); Iveric Bio, Optos (Lecture Fees/Speakers Bureau); Lumata Health, Recens Medical (Consultant/Advisor, Private Equity/Stock Holder); Spark Therapeutics (Consultant/Advisor, Lecture Fees/Speakers Bureau); Genentech (Consultant/Advisor, Lecture Fees/Speakers Bureau, Grant Support).