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Jaafar El Annan, Shlomit Schaal, Tongalp H. Tezel; Genetic Risk Factors for Age-related Macular Degeneration (AMD) can also be Predictive for the Functional and Anatomical Outcome of Intravitreal Anti-VEFG Treatment. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5255.
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© ARVO (1962-2015); The Authors (2016-present)
To determine whether a risk score derived from a combination of identified AMD risk haplotypes of complement factor H (CFH) and single nucleotide polymorphisms (SNPs) of C3, ARMS2, mitochondrial ND2 genes, along with the smoking history can be predictive for the functional and anatomic outcome of intravitreal bevacizumab treatment in exudative AMD.
Presence of eight SNPs of CFH, C3, ARMS2, and mitochondrial ND2 genes, including eight haplotypes of the CFH gene along with Y402H SNP were studied using polymerase chain reaction/fluorescent hybridization probe in 34 patients (42 eyes) with exudative AMD treated with intravitreal bevacizumab. Patients were assigned to a risk group (RG; I-V) depending upon their genotype and the history of smoking. Treatment algorithm included intravitreal bevacizumab (2.5 mg/0.1 ml) injections at every 12 weeks and full clinical and OCT exams at every 6 weeks. OCT data was corrected to normal diurnal variations of thickness using normograms obtained from an untreated AMD cohort before calculating the Standardized Volumetric Change Index (SVCI). Variations in SCVI over the treatment course were plotted and used to determine the anatomical response to the treatment. Similarly, change in LogMAR visual acuity was used to determine the functional outcome. Intergroup comparisons were done to determine the impact of genotypic variations on functional and anatomical outcome.
There were no age (p=0.13), gender (p=0.38), initial visual acuity (p=0.12), follow-up (p=0.31), OCT thickness (p=0.69) and SCVI (p=0.51) differences between RGs. The initial anatomic response was correlated with the pre-treatment macular volume (r=0.58, p=0.001) and comparable between all RGs (p=0.91). However, time-to-reach anatomical stability increased significantly as the risk category increases. (41 weeks for RG-I, indefinite for RG-5, p<0.001). Visual outcome followed a similar pattern with an average visual gain of 5 letters in RG-I and gradually increasing loss of vision for the rest of the RGs. The highest visual loss (10 letters) was observed in RG-5 (p<0.001).
The presence of high risk alleles of CFH, C3, ARMS2, ND2 indicate a poor response to anti-VEGF treatment. Patients expressing high-risk alleles require higher number of intravitreal injections to reach anatomical stability and are associated with poorer visual outcome.
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