Regression of Some High-risk Features of Age-related Macular Degeneration (AMD) in Patients Receiving Intensive Statin Treatment

Abstract

ImportanceAge-related macular degeneration (AMD) remains the leading cause of blindness in developed countries, and affects more than 150 million worldwide. Despite effective anti-angiogenic therapies for the less prevalent neovascular form of AMD, treatments are lacking for the more prevalent dry form. Similarities in risk factors and pathogenesis between AMD and atherosclerosis have led investigators to study the effects of statins on AMD incidence and progression with mixed results. A limitation of these studies has been the heterogeneity of AMD disease and the lack of standardization in statin dosage.ObjectiveWe were interested in studying the effects of high-dose statins, similar to those showing regression of atherosclerotic plaques, in AMD.DesignPilot multicenter open-label prospective clinical study of 26 patients with diagnosis of AMD and the presence of many large, soft drusenoid deposits. Patients received 80 mg of atorvastatin daily and were monitored at baseline and every 3 months with complete ophthalmologic exam, best corrected visual acuity (VA), fundus photographs, optical coherence tomography (OCT), and blood work (AST, ALT, CPK, total cholesterol, TSH, creatinine, as well as a pregnancy test for premenopausal women).ResultsTwenty-three subjects completed a minimum follow-up of 12 months. High-dose atorvastatin resulted in regression of drusen deposits associated with vision gain (+ 3.3 letters, p = 0.06) in 10 patients. No subjects progressed to advanced neovascular AMD.ConclusionsHigh-dose statins may result in resolution of drusenoid pigment epithelial detachments (PEDs) and improvement in VA, without atrophy or neovascularization in a high-risk subgroup of AMD patients. Confirmation from larger studies is warranted.

Statins and the progression of age-related macular degeneration in the United States

“…This is the largest observational study to specifically examine the effect of lipophilic statin dosage on progression to exudative AMD. In accordance with the findings of Vavvas et al we found that no patients taking very-high-dose lipophilic statins converted from non-exudative to exudative AMD despite an expected incidence of 1 to 2 patients, though this finding was not statistically significant [ 23 ]. We found no significant relationship between exposure to high-dose or low-dose lipophilic statins and progression to exudative AMD, nor did we find a difference in AMD progression between lipophilic and hydrophilic statins despite their relative pharmacokinetic differences [ 25 ].…”

Statins and the progression of age-related macular degeneration in the United States

“…This is the largest observational study to specifically examine the effect of lipophilic statin dosage on progression to exudative AMD. In accordance with the findings of Vavvas et al we found that no patients taking very-high-dose lipophilic statins converted from non-exudative to exudative AMD despite an expected incidence of 1 to 2 patients, though this finding was not statistically significant [ 23 ]. We found no significant relationship between exposure to high-dose or low-dose lipophilic statins and progression to exudative AMD, nor did we find a difference in AMD progression between lipophilic and hydrophilic statins despite their relative pharmacokinetic differences [ 25 ].…”

Using Advanced Bioinformatics Tools to Identify Novel Therapeutic Candidates for Age-Related Macular Degeneration

“… 80 One recent clinical trial reported vision gain with regression of drusen deposits in dry AMD patients that received a high dose of atorvastatin. 29 Our data further support evidence that FDA-approved lipid-lowering therapies may have the potential in halting the progression of the disease or restoring functionality in AMD patients. Both retrospective large scale studies on AMD incidences in patients taking such medications and eventually moving to larger clinical trials are needed to discern the precise effect of these drugs in vivo .…”

Medical Compliance of Fibrate and the Decreased Risk of Age-Related Macular Degeneration in Dyslipidemia-Related Diseases: A Population-Based Cohort Study

“…On the other hand, the mechanism of positive correlation of DM as well as male gender to AMD development is not clear and previous studies showed inconclusive results [ 37 , 38 ], thus further study may be needed. Interestingly, the use of statins did not lower the risk of AMD in the current study which is not in agreement with previous experience [ 12 , 13 , 14 ], but there were also some studies that showed an insignificant effect of statin on AMD prevention [ 39 , 40 ]. Maybe MPR also plays a role in the relationship between statins and AMD occurrence.…”

Statins and the progression of age-related macular degeneration in the United States

“…This is the largest observational study to specifically examine the effect of lipophilic statin dosage on progression to exudative AMD. In accordance with the findings of Vavvas et al we found that no patients taking very-high-dose lipophilic statins converted from non-exudative to exudative AMD despite an expected incidence of 1 to 2 patients, though this finding was not statistically significant [ 23 ]. We found no significant relationship between exposure to high-dose or low-dose lipophilic statins and progression to exudative AMD, nor did we find a difference in AMD progression between lipophilic and hydrophilic statins despite their relative pharmacokinetic differences [ 25 ].…”

Using Advanced Bioinformatics Tools to Identify Novel Therapeutic Candidates for Age-Related Macular Degeneration

“… 80 One recent clinical trial reported vision gain with regression of drusen deposits in dry AMD patients that received a high dose of atorvastatin. 29 Our data further support evidence that FDA-approved lipid-lowering therapies may have the potential in halting the progression of the disease or restoring functionality in AMD patients. Both retrospective large scale studies on AMD incidences in patients taking such medications and eventually moving to larger clinical trials are needed to discern the precise effect of these drugs in vivo .…”

Medical Compliance of Fibrate and the Decreased Risk of Age-Related Macular Degeneration in Dyslipidemia-Related Diseases: A Population-Based Cohort Study

“…On the other hand, the mechanism of positive correlation of DM as well as male gender to AMD development is not clear and previous studies showed inconclusive results [ 37 , 38 ], thus further study may be needed. Interestingly, the use of statins did not lower the risk of AMD in the current study which is not in agreement with previous experience [ 12 , 13 , 14 ], but there were also some studies that showed an insignificant effect of statin on AMD prevention [ 39 , 40 ]. Maybe MPR also plays a role in the relationship between statins and AMD occurrence.…”

Statins and the progression of age-related macular degeneration in the United States

“…This is the largest observational study to specifically examine the effect of lipophilic statin dosage on progression to exudative AMD. In accordance with the findings of Vavvas et al we found that no patients taking very-high-dose lipophilic statins converted from non-exudative to exudative AMD despite an expected incidence of 1 to 2 patients, though this finding was not statistically significant [ 23 ]. We found no significant relationship between exposure to high-dose or low-dose lipophilic statins and progression to exudative AMD, nor did we find a difference in AMD progression between lipophilic and hydrophilic statins despite their relative pharmacokinetic differences [ 25 ].…”

Using Advanced Bioinformatics Tools to Identify Novel Therapeutic Candidates for Age-Related Macular Degeneration

“… 80 One recent clinical trial reported vision gain with regression of drusen deposits in dry AMD patients that received a high dose of atorvastatin. 29 Our data further support evidence that FDA-approved lipid-lowering therapies may have the potential in halting the progression of the disease or restoring functionality in AMD patients. Both retrospective large scale studies on AMD incidences in patients taking such medications and eventually moving to larger clinical trials are needed to discern the precise effect of these drugs in vivo .…”

Medical Compliance of Fibrate and the Decreased Risk of Age-Related Macular Degeneration in Dyslipidemia-Related Diseases: A Population-Based Cohort Study

“…On the other hand, the mechanism of positive correlation of DM as well as male gender to AMD development is not clear and previous studies showed inconclusive results [ 37 , 38 ], thus further study may be needed. Interestingly, the use of statins did not lower the risk of AMD in the current study which is not in agreement with previous experience [ 12 , 13 , 14 ], but there were also some studies that showed an insignificant effect of statin on AMD prevention [ 39 , 40 ]. Maybe MPR also plays a role in the relationship between statins and AMD occurrence.…”