MyVisionTest News Archive
Apr 24, 2009
Response to Lucentis for wet AMD differs according to CFH genotype
Exudative AMD patients with the compliment factor H (CFH Y402H) high risk genotype (CC) received approximately one more Lucentis injection over a 9 month follow-up period than persons who do not have the high risk genotype.
Genetic studies have made advancements in establishing the molecular cause of AMD. Two genes that seem to greatly influence the risk of developing AMD are the complement factor H (CFH) gene and a locus on chromosome 10 with an unknown function referred to as LOC387715. Other genes, including those regulating complement 2 (C2), complement 3 (C3), and complement factor B also influence the risk of developing AMD.
Complement factor H is an important regulator of the complement system. CFH specifically inhibits the alternative complement cascade but also regulates the common pathway. An aberration in the function or expression of the CFH protein could interfere with down-regulation of the alternative pathway and lead to excessive inflammation and damage of the tissue. CFH is implicated in all stages of AMD (from early hallmarks such as drusen to vision-disabling late AMD) and both major subtypes (wet and dry). A meta-analysis of eight studies assessing association between the CFH Y402H polymorphism and AMD found that those persons having the high risk CC genotype were roughly 6 times more likely to have AMD than patients with the TT genotype. It was calculated that individuals homozygous for the CFH Y402H polymorphism (CC genotype) have a 48% risk of developing late AMD by age 95 years while this risk does not exceed 22% for non-carriers (TT genotype). The association of both wet and dry AMD with CFH suggests a common pathogenesis involving the complement system.
Recently, several studies have found that the CFH genotype can determine the benefit of treatments directed at AMD. In June 2008, the AREDS study group reported that the CFH genotype determines the benefit of the AREDS vitamin-mineral supplement on AMD progression. In March 2009, researchers reported that weekly fish consumption decreases the risk of late AMD in persons with the high-risk CC CFH genotype but not in persons with other CFH genotypes.
The current study is a retrospective review of 156 patients with exudative AMD treated with intravitreal Lucentis monotherapy. AMD phenotypes were characterised by clinical examination, visual acuity, fundus photography, fluorescein angiography and injection timing. Patients received intravitreal ranibizumab injections as part of routine ophthalmological care and were followed for a minimum of 9 months. Each patient was genotyped for the single nucleotide polymorphism rs1061170 (Y402H) in the CFH gene.
Baseline lesion size and angiographic type, as well as mean visual acuities at baseline, 6 months, and 9 months were similar among the three CFH genotypes. Over 9 months, patients with both risk alleles received approximately one more injection (p = 0.09). In a recurrent event analysis, patients homozygous for the CFH Y402H risk allele had a 37% significantly higher risk of requiring additional Lucentis injections (p = 0.04).
The investigators conclude that in this study cohort, the response to treatment of AMD with Lucentis differed according to CFH genotype, suggesting that determining patients' CFH genotype may be helpful in the future in tailoring treatment for exudative AMD with intravitreal Lucentis.
WHAT IT MEANS TO YOU: It is clear that genotype plays a major role in determining who will develop AMD. And now there is growing evidence that one's genotype can have a significant effect on one's response to therapy. The nascent field of pharamacogenetics is devoted to understanding the relationship between drug therapy and genetics. Macular degeneration is shaping up to be a textbook example of how genetics can significantly influence response to drug therapy. We now have evidence that treatment response to both Lucentis and Avastin is influenced by CFH genotype. There is similar evidence that genotype plays a role in the effectiveness of the AREDS vitamin-mineral supplement and of fish consumption. It is clear that knowing one's genotype can be very helpful not only in knowing the risk of contracting AMD, but of how aggressively it needs to be treated once it occurs.
Read more...
Br J Ophthalmol. 2009;93:610-613
Tags: wet AMD, genetics, complement, Lucentis, pharmacogenetics
Exudative AMD patients with the compliment factor H (CFH Y402H) high risk genotype (CC) received approximately one more Lucentis injection over a 9 month follow-up period than persons who do not have the high risk genotype. Genetic studies have made advancements in establishing the molecular cause of AMD. Two genes that seem to greatly influence the risk of developing AMD are the complement factor H (CFH) gene and a locus on chromosome 10 with an unknown function referred to as LOC387715. Other genes, including those regulating complement 2 (C2), complement 3 (C3), and complement factor B also influence the risk of developing AMD.
Recently, several studies have found that the CFH genotype can determine the benefit of treatments directed at AMD. In June 2008, the AREDS study group reported that the CFH genotype determines the benefit of the AREDS vitamin-mineral supplement on AMD progression. In March 2009, researchers reported that weekly fish consumption decreases the risk of late AMD in persons with the high-risk CC CFH genotype but not in persons with other CFH genotypes.
The current study is a retrospective review of 156 patients with exudative AMD treated with intravitreal Lucentis monotherapy. AMD phenotypes were characterised by clinical examination, visual acuity, fundus photography, fluorescein angiography and injection timing. Patients received intravitreal ranibizumab injections as part of routine ophthalmological care and were followed for a minimum of 9 months. Each patient was genotyped for the single nucleotide polymorphism rs1061170 (Y402H) in the CFH gene.
Baseline lesion size and angiographic type, as well as mean visual acuities at baseline, 6 months, and 9 months were similar among the three CFH genotypes. Over 9 months, patients with both risk alleles received approximately one more injection (p = 0.09). In a recurrent event analysis, patients homozygous for the CFH Y402H risk allele had a 37% significantly higher risk of requiring additional Lucentis injections (p = 0.04).
The investigators conclude that in this study cohort, the response to treatment of AMD with Lucentis differed according to CFH genotype, suggesting that determining patients' CFH genotype may be helpful in the future in tailoring treatment for exudative AMD with intravitreal Lucentis.
WHAT IT MEANS TO YOU: It is clear that genotype plays a major role in determining who will develop AMD. And now there is growing evidence that one's genotype can have a significant effect on one's response to therapy. The nascent field of pharamacogenetics is devoted to understanding the relationship between drug therapy and genetics. Macular degeneration is shaping up to be a textbook example of how genetics can significantly influence response to drug therapy. We now have evidence that treatment response to both Lucentis and Avastin is influenced by CFH genotype. There is similar evidence that genotype plays a role in the effectiveness of the AREDS vitamin-mineral supplement and of fish consumption. It is clear that knowing one's genotype can be very helpful not only in knowing the risk of contracting AMD, but of how aggressively it needs to be treated once it occurs.
Read more...
Br J Ophthalmol. 2009;93:610-613
