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S. J. Teper, E. Wylegala, J. Pilat; Joint Effect of A69S LOC387715 and Y402H CFH on Response to Ranibizumab in AMD. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3444.
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© ARVO (1962-2015); The Authors (2016-present)
To assess putative effect of gene variants A69S LOC387715 and Y402H complement factor H (CFH) on treatment results in patients with subretinal neovascularization secondary to age-related macular degeneration (AMD).
80 patients with neovascular AMD were treated with ranibizumab for 12 months. All patients underwent fluorescein angiography and optical coherence tomography (OCT) at baseline and close-up of the study. Every month patients were examined with OCT to determine the necessity of retreatment. SUSTAIN study criteria were used - reinjection was done if a patient lost 5 letters or gained >100 µm in retinal thickness - in central subfield of macular thickness map. Best corrected visual acuity was measured with ETDRS charts. Fast Macular Thickness Map acquisition protocol (Zeiss Stratus III) was performed to gain quantitative OCT data. A69S variant of LOC387715 and Y402H variant of CFH were confirmed with gene sequencing after previous DNA isolation from blood and amplification with polymerase chain reaction (PCR).
Following gene sequencing results were obtained: 2 alleles/1 allele/0 alleles A69S LOC 387715 had 25/34/10 patients respectively, alleles/1 allele/0 alleles Y402H CFH had 29/39/12 patients. Mean central subfield retinal thickness (CSRT) at baseline was 324.0±90.7 µm, while at close-up - 222.4±66.4 µm. Mean BCVA before study was 42.2±14.73 letters and 46.7±16.6 at the end. To assess joint effect of A69S LOC387715 and Y402H CFH BCVA and CSRT were measured in 5 groups.BCVA [letters] before/at close-up: 4 risk alleles (10 patients) - 41.16±15.34/39.83±13.47, 3 risk alleles (25 patients) - 41.82±16.39/42.77±16.81, 2 risk alleles (25 patients) - 41.88±15.1/48.84±17.47, 1 risk allele (16 patients) - 40.6±13.29/47.13±16.04, no risk alleles (4 patients) - 48.67±11.01/56±13.23.CSRT [µm] before/at close-up: 4 risk alleles - 330.33±116.21/274.83±129.6, 3 risk alleles - 305.54±58.71/205.59±51.19, 2 risk alleles - 342.56±105.33/227±69.54, 1 risk allele - 325.33±102.02/221.8±63.61, no risk alleles - 275.33±45.78/238.33±27.79.Patients with 3 -4 risk alleles gained 0.46±8.23 letters, while patients with 0-2 risk alleles gained 7±8.36 letters. The difference was statistically significant (p<0.03).
A69S LOC387715 and Y402H CFH polymorphisms seem not only play role in etiology of age-related macular degeneration but also affect the results of treatment. It can be either related to less effective anti-VEGF agent activity or to more aggressive form of the disease.
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