Table 1.
Summary of findings supporting the positive or negative association between statins and AMD.
| Reference | Statin group | Description of the Study | Scenario | Primary outcomes assessed | Subjects | Conclusion | Potential association |
|---|---|---|---|---|---|---|---|
| Tian et al., 2017 [62] | Atorvastatin 50 µM | The study describes the action of atorvastatin on the phagocytic function of ARPE-19 cells and on the inflammatory effects induced by crystals of cholesterol and ox-LDL | Non-clinical | Phagocytic function of ARPE-19 cells and induction of interleukins IL-6 and IL-8 | ARPE-19 cell line | Statins help to preserve the phagocytic function of the RPE while also exhibiting anti-inflammatory properties | Positive |
| Barbosa et al., 2014 [74] | Not specified | Patients were asked if they carried a diagnosis of AMD, if they used any type of statin agents without regard to dose, and about their comorbidities and health-related behaviors, such as smoking. | Clinical | Correlated the number of long-term users of statins and the number of self-reported AMD patients after adjustment for confounding factors | 5604 participants older than 40 years | Individuals of 68 years or older who were classified as long-term users of statins had less self-reported AMD after adjustment for confounding factors | Positive |
| Klein et al., 2003 [75] | Not specified | Questionnaire approach examining the association of statin use with a 5-year incidence of AMD in a large population-based epidemiologic study | Clinical | Chances of having soft drusen or late AMD among those who started statins during the previous 5 years as compared with patients who never took statins | 2780 healthy people aged 48–91 years old | Those who started statins during the previous 5 years were less likely to have soft drusen and large soft drusen and less likely to have late AMD over the follow-up period | Positive |
| Fong et al., 2010 [76] | Not specified | Drug use information was obtained using computerized databases of newly diagnosed AMD cases and healthy controls who had seen an ophthalmologist during a period of one year | Clinical | Prevalence of neovascular AMD | 719 patients older than 60 years newly diagnosed with exudative AMD | The work showed a statin protective effect against neovascular AMD | Positive |
| Ma et al., 2015 [77] | Not specified | A systematic search of the PubMed, EMBASE, and ISI web of science databases was used to identify eligible published literatures | Clinical | Evaluated the association between statin use and the risk of early and exudative AMD. | A total of 14 studies met the inclusion criteria and were included in this meta-analysis | For early AMD, statin use significantly reduced the risk. At the late stage, a significant protective association of statin use with exudative AMD, in contrast with the absent association between statins and geographic atrophy | Positive |
| Vavvas et al., 2016 [78] | 80 mg of Atorvastatin | Patients with a diagnosis of AMD, the presence of many large, soft drusenoid deposits, and who then received high-dose atorvastatin for 12 months were evaluated | Clinical | Regression of drusen deposits, vision gained, and progression to advanced neovascular AMD | 26 patients with a diagnosis of AMD | The group presented regression of drusen associated with vision gain in 10 patients. None of the study’s patients progressed to advanced neovascular AMD | Positive |
| Guymer et al., 2013 [79] | 40 mg of Simvastatin | This was a 3-year study of simvastatin in participants with nonadvanced AMD in at least one eye, considered at high risk of progression toward advanced. | Clinical | Progression of AMD either to advanced AMD or in severity of non-advanced AMD | 114 participants aged 53–91 years, with either bilateral intermediate AMD or unilateral non-advanced AMD (with advanced AMD in fellow eye), BCVA 20/60 in at least one eye, and a normal lipid profile | The cumulative AMD progression rates were higher in the placebo as compared to the simvastatin group | Positive |
| Al-Holou, 2015 [80] | Not specified | Age-adjusted proportional hazards regression models were used to evaluate the association of statin use with progression to late AMD | Clinical | Baseline and annual stereoscopic fundus photographs were assessed centrally for the development of late AMD, either neovascular AMD or geographic atrophy | 3791 participants of whom 1659 were already previous statin users | There was no statistically significant evidence that statins had a beneficial effect in slowing AMD progression or in preventing the disease from progressing to the late stage | Negative |
| Maguire et al., 2009 [81] | Not specified | Patients were asked about their use of statins on the day of ophthalmological exams | Clinical | Development of advanced AMD, choroidal neovascularization, and endpoint geographic atrophy. | 764 patients with bilateral large drusen | Statin use did not show a strong protective effect on the development of advanced AMD among patients with bilateral large drusen | Negative |
| VanderBeek et al., 2013 [82] | Not specified | Prescription for statins within a 24-month look-back period and outpatient lipid lab values were reviewed using an insurance database. Cox regression analysis was performed to determine whether statin use was associated with the development of non-exudative or exudative AMD, or progression from non-exudative to exudative AMD | Clinical | To determine if statins are associated with the development or progression of AMD | 107,007 individuals aged ≥60 years who were enrolled for ≥2 years and had ≥1 visit(s) to an eye provider | In those with elevated lipid levels, >1 year of statin use was associated with an increased hazard for exudative AMD | Negative |
| Shalev et al., 2011 [83] | Not specified | The organization’s central computerized database was used to collect information on incident AMD cases that were already on a statin | Clinical | To investigate the association between persistent use of statins and the risk of AMD | 108,973 individuals aged 55 or older who began statin therapy between 1998 and 2006 in a large health organization in Israel | The crude incidence density rate of AMD among patients in the lowest quintile of the proportion of days covered was comparable to that of patients in the highest quintile. Moreover, after adjustment for potential confounders, patients with persistent use of statins had a risk ratio for AMD comparable with patients in the lowest proportion of days covered | Negative |
| Gehlbach et al., 2016 [73] | 20 or 40 mg of Simvastatin | Meta-analysis in the form of a Cochrane system-wide review that identified only two randomized controlled trials from the literature that met the Cochrane inclusion criteria. | Clinical | To examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and progression of AMD | Randomized controlled trials and quasi-randomized trials that compared statins with other treatments, no treatment, or placebo in people who were diagnosed as having the early stages of AMD | Evidence from currently available randomized controlled trials is insufficient to conclude that statins have a role in preventing or delaying the onset or progression of AMD | Negative |
| Martini et al., 1991 [84] | 20 mg of Simvastatin | Clinical trial in which participants with early-stage AMD received simvastatin or placebo for only 3 months | Clinical | Final visual acuity | 30 participants with early-stage AMD | There was no difference between the simvastatin and the placebo therapy in terms of visual acuity | Negative |
ox-LDL: oxidized low-density lipoproteins; AMD: age-related macular degeneration; BCVA: best corrected visual acuity; RPE: retinal pigment epithelium.