MD Research News Issue 92

Tuesday August 7, 2012

This free weekly bulletin lists the latest published research articles on macular degeneration (MD) as indexed in the NCBI, PubMed (Medline) and Entrez (GenBank) databases. These articles were identified by a search using the key term “macular degeneration”. If you have not already subscribed, please email Rob Cummins at [email protected] with „Subscribe to MD Research News‟ in the subject line, and your name and address in the body of the email. You may unsubscribe at any time by an email to the above address with your „unsubscribe‟ request.

Drug treatment PLoS One. 2012;7(7):e42014. Epub 2012 Jul 25. Impact of Loading Phase, Initial Response and CFH Genotype on the Long-Term Outcome of Treatment for Neovascular Age-Related Macular Degeneration. Menghini M, Kloeckener-Gruissem B, Fleischhauer J, Kurz-Levin MM, Sutter FK, Berger W, Barthelmes D. Department of Ophthalmology, University Hospital of Zurich, Zurich, Switzerland. OBJECTIVE: Factors influencing the outcome of anti-VEGF treatment in neovascular AMD are still investigated. We analyzed the impact of a loading phase, the significance of an initial response for the longterm and the effect of the CFH polymorphism (p.His402Tyr) on treatment outcome. METHODS: Patients treated with ranibizumab for neovascular AMD were analyzed over a period of 24 months by assessing effects of loading phase, initial response and genotype of CFH rs1061170 (c.1204C>T, p.His402Tyr). RESULTS: 204 eyes were included. A change of +5.0 [-1;+11] letters and +1.5 [-5.5;+9.5] was observed with a median of 4 [3]; [7] and 10 [7]; [14] ranibizumab injections during 12 and 24 months, respectively. Loading phase was no significant predictor for treatment as VA outcome in eyes with and without loading phase was similar (p = 0.846 and p = 0.729) at 12 and 24 months. In contrast, initial response was a significant predictor for improving vision of 5 or more letters at 12 (p = 0.001; OR = 6.75) and 24 months (p =  0.01; OR = 4.66). Furthermore, the CT genotype at CFH rs1061170 was identified as a significant predictor for a favorable VA outcome at 12 and 24 months (OR = 6.75, p = 0.001 and OR = 4.66, p = 0.01). CONCLUSIONS: Our data suggest that clinical decisions regarding treatment may be guided by observing patients' initial response as well as their genotype of SNP rs1061170, while the criterion of loading phase may not bear the customary value. PMID: 22848690 [PubMed - in process] PMCID: PMC3405003 Free PMC Article

Ophthalmology. 2012 Jul 26. [Epub ahead of print] Cumulative Effect of Risk Alleles in CFH, ARMS2, and VEGFA on the Response to Ranibizumab Treatment in Age-Related Macular Degeneration. Smailhodzic D, Muether PS, Chen J, Kwestro A, Zhang AY, Omar A, Van de Ven JP, Keunen JE, Kirchhof

B, Hoyng CB, Klevering BJ, Koenekoop RK, Fauser S, den Hollander AI. Department of Ophthalmology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. PURPOSE: Intravitreal ranibizumab injections currently are the standard treatment for neovascular agerelated macular degeneration (AMD). However, a broad range of response rates have been observed, the reasons for which are poorly understood. This pharmacogenetic study evaluated the impact of high-risk alleles in CFH, ARMS2, VEGFA, vascular endothelial growth factor (VEGF) receptor KDR, and genes involved in angiogenesis (LRP5, FZD4) on the response to ranibizumab treatment and on the age of treatment onset. In contrast to previous studies, the data were stratified according to the number of highrisk alleles to enable the study of the combined effects of these genotypes on the treatment response. DESIGN: Case series study. PARTICIPANTS: A cohort of 420 eyes of 397 neovascular AMD patients. METHODS: The change in visual acuity (VA) between baseline and after 3 ranibizumab injections was calculated. Genotyping of single nucleotide polymorphisms in the CFH, ARMS2, VEGFA, KDR, LPR5, and FZD4 genes was performed. Associations were assessed using linear mixed models. MAIN OUTCOME MEASURES: The VA change after 3 ranibizumab injections and the age of neovascular disease onset. RESULTS: After ranibizumab treatment, AMD patients without risk alleles in the CFH and ARMS2 genes (4.8%) demonstrated a mean VA improvement of 10 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, whereas no VA improvement was observed in AMD patients with 4 CFH and ARMS2 risk alleles (6.9%; P = 0.014). Patients with 4 high-risk alleles in CFH and ARMS2 were 5.2 years younger than patients with 1 or 2 risk alleles, respectively (63.5%; P