Statins for age-related macular degeneration

Abstract

Background Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries (Congdon 2003). Recent epidemiologic, genetic and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. Objectives To examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and/or progression of AMD. Search strategy We searched CENTRAL in The Cochrane Library, MEDLINE, EMBASE and LILACS on 30 April 2009 and the WHO International Clinical Trials Registry Platform on 11 May 2009. We searched reference lists and the Science Citation Index. There were no language or date restrictions in the search for trials. Selection criteria We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD. Data collection and analysis Two authors independently evaluated the search results against the selection criteria. Two Italian speaking colleagues extracted data. One author entered data. We did not perform a meta-analysis because only one completed RCT was identified. Main results Two studies met the selection criteria. One trial reported insufficient details to assess the risk of bias; the other trial is ongoing. Of the completed trial, the analyses of 30 participants did not show a statistically significant difference between the simvastatin and the placebo arm in visual acuity at three months of treatment (decimal visual acuity 0.21± 0.56 in simvastatin and 0.19± 0.40 in placebo arm) or 45 days after the completion of treatment (decimal visual acuity 0.20± 0.50 in simvastatin and 0.19± 0.48 in placebo arm). The lens and retina status were unchanged during and after the treatment period for both groups. Of the ongoing trial, the preliminary analyses of 42 participants who completed 12 months follow-up did not show a statistically significant difference between the simvastatin and the placebo arm in visual acuity, drusen score or visual function (effect estimates and confidence intervals were not available). We contacted the investigators and will update the review as data become available. Authors' conclusions Evidence from currently available RCTs was insufficient to conclude that statins have any role in preventing or delaying the onset or progression of AMD.

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

“…AMD is a heterogeneous disease, with several different phenotypes, including types and size of drusen ( Miller, 2013 ). Prior epidemiological studies examining the role of statins in AMD ( Hall et al, 2001 , Gehlbach and Li, 2009 , Gehlbach et al, 2015 , Guymer et al, 2013 , VanderBeek et al, 2013 , Cougnard-Gregoire et al, 2014 , Klein et al, 2014a , Klein et al, 2007 , Tan et al, 2007 ) did not stratify or distinguish patients based on AMD subtype. It is unlikely that statins would have across-the-board effectiveness in a heterogeneous disease, and for this reason we focused on patients with large soft drusen and drusenoid PEDs, which are known risk factors for progression to advanced disease.…”

“…In addition, they increase liver LDL receptors levels ( Bilheimer et al, 1983 ), reduce apo B synthesis ( Arad et al, 1990 ) and suppress prenylation (the addition of hydrophobic molecules to a protein that is a physiologic process that control localization and function) ( Kino et al, 2005 ). Multiple epidemiological studies have examined this relationship with conflicting data ( Gehlbach et al, 2009 ). A 2015 Cochrane report ( Gehlbach et al, 2015 ) concluded that “[evidence is] insufficient to conclude if statins have a role in preventing or delaying the onset or progression of AMD.” A small, proof-of-concept, randomized, placebo-controlled study of the effect of simvastatin on the course of AMD was recently published, and suggested that simvastatin at 40 mg (equivalent to 20 mg atorvastatin) daily may slow progression of early/intermediate AMD, especially for those with the at-risk complement factor H (CFH) genotype CC (Y402H) ( Guymer et al, 2013 ).…”

“…A major limitation in almost all studies thus far is the large heterogeneity of AMD disease (more than 100 at-risk genes and several phenotypes) ( Miller, 2013 , Fritsche et al, 2015 ) and lack of standardization in statin dosage ( Gehlbach and Li, 2009 , Gehlbach et al, 2015 ) or lipophilicity ( Wu et al, 2010 , Chitose et al, 2014 , Fong, 2014 ). There is clear evidence from the cardiovascular literature that statin dose does matter ( Cannon et al, 2004 , Pitt et al, 1999 ).…”

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

“…AMD is a heterogeneous disease, with several different phenotypes, including types and size of drusen ( Miller, 2013 ). Prior epidemiological studies examining the role of statins in AMD ( Hall et al, 2001 , Gehlbach and Li, 2009 , Gehlbach et al, 2015 , Guymer et al, 2013 , VanderBeek et al, 2013 , Cougnard-Gregoire et al, 2014 , Klein et al, 2014a , Klein et al, 2007 , Tan et al, 2007 ) did not stratify or distinguish patients based on AMD subtype. It is unlikely that statins would have across-the-board effectiveness in a heterogeneous disease, and for this reason we focused on patients with large soft drusen and drusenoid PEDs, which are known risk factors for progression to advanced disease.…”

“…In addition, they increase liver LDL receptors levels ( Bilheimer et al, 1983 ), reduce apo B synthesis ( Arad et al, 1990 ) and suppress prenylation (the addition of hydrophobic molecules to a protein that is a physiologic process that control localization and function) ( Kino et al, 2005 ). Multiple epidemiological studies have examined this relationship with conflicting data ( Gehlbach et al, 2009 ). A 2015 Cochrane report ( Gehlbach et al, 2015 ) concluded that “[evidence is] insufficient to conclude if statins have a role in preventing or delaying the onset or progression of AMD.” A small, proof-of-concept, randomized, placebo-controlled study of the effect of simvastatin on the course of AMD was recently published, and suggested that simvastatin at 40 mg (equivalent to 20 mg atorvastatin) daily may slow progression of early/intermediate AMD, especially for those with the at-risk complement factor H (CFH) genotype CC (Y402H) ( Guymer et al, 2013 ).…”

“…A major limitation in almost all studies thus far is the large heterogeneity of AMD disease (more than 100 at-risk genes and several phenotypes) ( Miller, 2013 , Fritsche et al, 2015 ) and lack of standardization in statin dosage ( Gehlbach and Li, 2009 , Gehlbach et al, 2015 ) or lipophilicity ( Wu et al, 2010 , Chitose et al, 2014 , Fong, 2014 ). There is clear evidence from the cardiovascular literature that statin dose does matter ( Cannon et al, 2004 , Pitt et al, 1999 ).…”

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

“…AMD is a heterogeneous disease, with several different phenotypes, including types and size of drusen ( Miller, 2013 ). Prior epidemiological studies examining the role of statins in AMD ( Hall et al, 2001 , Gehlbach and Li, 2009 , Gehlbach et al, 2015 , Guymer et al, 2013 , VanderBeek et al, 2013 , Cougnard-Gregoire et al, 2014 , Klein et al, 2014a , Klein et al, 2007 , Tan et al, 2007 ) did not stratify or distinguish patients based on AMD subtype. It is unlikely that statins would have across-the-board effectiveness in a heterogeneous disease, and for this reason we focused on patients with large soft drusen and drusenoid PEDs, which are known risk factors for progression to advanced disease.…”

“…In addition, they increase liver LDL receptors levels ( Bilheimer et al, 1983 ), reduce apo B synthesis ( Arad et al, 1990 ) and suppress prenylation (the addition of hydrophobic molecules to a protein that is a physiologic process that control localization and function) ( Kino et al, 2005 ). Multiple epidemiological studies have examined this relationship with conflicting data ( Gehlbach et al, 2009 ). A 2015 Cochrane report ( Gehlbach et al, 2015 ) concluded that “[evidence is] insufficient to conclude if statins have a role in preventing or delaying the onset or progression of AMD.” A small, proof-of-concept, randomized, placebo-controlled study of the effect of simvastatin on the course of AMD was recently published, and suggested that simvastatin at 40 mg (equivalent to 20 mg atorvastatin) daily may slow progression of early/intermediate AMD, especially for those with the at-risk complement factor H (CFH) genotype CC (Y402H) ( Guymer et al, 2013 ).…”

“…A major limitation in almost all studies thus far is the large heterogeneity of AMD disease (more than 100 at-risk genes and several phenotypes) ( Miller, 2013 , Fritsche et al, 2015 ) and lack of standardization in statin dosage ( Gehlbach and Li, 2009 , Gehlbach et al, 2015 ) or lipophilicity ( Wu et al, 2010 , Chitose et al, 2014 , Fong, 2014 ). There is clear evidence from the cardiovascular literature that statin dose does matter ( Cannon et al, 2004 , Pitt et al, 1999 ).…”

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

“…AMD is a heterogeneous disease, with several different phenotypes, including types and size of drusen ( Miller, 2013 ). Prior epidemiological studies examining the role of statins in AMD ( Hall et al, 2001 , Gehlbach and Li, 2009 , Gehlbach et al, 2015 , Guymer et al, 2013 , VanderBeek et al, 2013 , Cougnard-Gregoire et al, 2014 , Klein et al, 2014a , Klein et al, 2007 , Tan et al, 2007 ) did not stratify or distinguish patients based on AMD subtype. It is unlikely that statins would have across-the-board effectiveness in a heterogeneous disease, and for this reason we focused on patients with large soft drusen and drusenoid PEDs, which are known risk factors for progression to advanced disease.…”

“…In addition, they increase liver LDL receptors levels ( Bilheimer et al, 1983 ), reduce apo B synthesis ( Arad et al, 1990 ) and suppress prenylation (the addition of hydrophobic molecules to a protein that is a physiologic process that control localization and function) ( Kino et al, 2005 ). Multiple epidemiological studies have examined this relationship with conflicting data ( Gehlbach et al, 2009 ). A 2015 Cochrane report ( Gehlbach et al, 2015 ) concluded that “[evidence is] insufficient to conclude if statins have a role in preventing or delaying the onset or progression of AMD.” A small, proof-of-concept, randomized, placebo-controlled study of the effect of simvastatin on the course of AMD was recently published, and suggested that simvastatin at 40 mg (equivalent to 20 mg atorvastatin) daily may slow progression of early/intermediate AMD, especially for those with the at-risk complement factor H (CFH) genotype CC (Y402H) ( Guymer et al, 2013 ).…”

“…A major limitation in almost all studies thus far is the large heterogeneity of AMD disease (more than 100 at-risk genes and several phenotypes) ( Miller, 2013 , Fritsche et al, 2015 ) and lack of standardization in statin dosage ( Gehlbach and Li, 2009 , Gehlbach et al, 2015 ) or lipophilicity ( Wu et al, 2010 , Chitose et al, 2014 , Fong, 2014 ). There is clear evidence from the cardiovascular literature that statin dose does matter ( Cannon et al, 2004 , Pitt et al, 1999 ).…”