Influence of CFH, HTRA1 and ARMS2 polymorphisms in the response to intravitreal ranibizumab treatment for wet age-related macular degeneration in a Spanish population.

AIM: To determine whether gene polymorphisms of the major genetic risk loci for age-related macular degeneration (AMD): ARMS2 (rs10490923), the complement factor H (CFH) (rs1410996) and HTRA1 (rs11200638) influence the response to a treatment regimen with ranibizumab for exudative AMD. METHODS: This study included 100 patients (100 eyes) with exudative AMD. Patients underwent a treatment with ranibizumab injections monthly during three months. Reinjections were made when the best corrected visual acuity (BCVA) decrease five letters (ETDRS) or central subfield retinal thickness gained 100 µm in optical coherence tomography image. Genotypes (rs10490923, rs1410996 and rs11200638) were analyzed using TaqMan probes or polymerase chain reaction-restricted fragment length polymorphisms analysis. RESULTS: There were no statistically significant differences in allelic distribution of CFH (rs1410996), ARMS2 (rs10490923) and HTRA1 (rs11200638) polymorphisms regarding to response to ranibizumab treatment. CONCLUSION: Ranibizumab treatment response is not related to CFH (rs1410996), ARMS2 (rs10490923) and HTRA1 (rs11200638) poymorphisms.

Association of Lysyl Oxidase-Like 1 Gene Polymorphisms in Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma in a Spanish Population.

PURPOSE: To evaluate the association of the lysyl oxidase-like 1 (LOXL1) single nucleotide polymorphisms (SNPs) in a Spanish population with pseudoexfoliation syndrome (XFS) and pseudoexfoliation glaucoma (XFG). MATERIALS AND METHODS: The present case-control study included 100 Spanish patients (60 patients with XFS and 40 patients with XFG) and 90 control subjects. Genotypes of the three single nucleotide polymorphisms of LOXL1 (rs1048661, rs3825942, and rs2165241) were analyzed with direct sequencing. RESULTS: The G allele and the GG genotype of SNP rs3825942 were detected at a statistically higher frequency in pseudoexfoliation patients than in control subjects (p = 3.36 × 10(-5), OR = 5.71, 95% CI: 2.30-14.18; p = 3.38 × 10(-5), OR = 6.91, 95% CI: 2.51-19.03 respectively). The T allele and the TT genotype of SNP rs2165241 presented at significantly higher frequencies in pseudoexfoliation patients than in controls (p = 2.50 × 10(-4), OR = 2.18, 95% CI: 1.43-3.33; p = 1.21 × 10(-2), OR = 2.13, 95% CI: 1.75-3.85 respectively). No significant association between XFS/XFG and the rs1048661 was observed. The GGT haplotype composed of all three risk alleles was determined to be significantly associated with pseudoexfoliation. The genotypic and allelic distributions of the three SNPs were similar between XFS and XFG. CONCLUSIONS: This is the first study associating two SNPs of LOXL1 (rs3825942 and rs2165241) and XFS/XFG in a Spanish population, confirming findings in patients from Europe. However rs1048661 SNP did not show an association with XFS.

Predictive value of VEGF A and VEGFR2 polymorphisms in the response to intravitreal ranibizumab treatment for wet AMD.

BACKGROUND: To determine whether gene polymorphisms of the vascular endothelial growth factor A (VEGF A) and its receptor (VEGFR) influence the response to a variable-dosing treatment regimen with ranibizumab for age-related macular degeneration. METHODS: This prospective cohort study included 94 patients (94 eyes) with exudative age-related macular degeneration (AMD) treated with ranibizumab. Patients underwent a 1-year treatment as in the Study of Ranibizumab in Patients with Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration (SUSTAIN). Injections were administered monthly during 3 months to all the patients diagnosed of neovascular AMD; reinjections were made when a patient lost 5 letters on the Early Treatment Diabetic Retinopathy Study chart or gained 100 µm in central subfield retinal thickness measured by OCT. Genotypes (VEGF A (rs 699947, rs833061) and VEGFR (rs 2071559)) were analyzed using TaqMan probes. Best-corrected visual acuity (BCVA), subjective improvement, and macular thickness measured with OCT values were compared with VEGF A and VEGFR genotypes. Multiple regression analysis was used to assess the statistical significance. RESULTS: We found statistically significant differences in allelic distribution of VEGF A rs833061 polymorphism in relation with the response to intravitreal ranibizumab regarding to visual acuity improvement [p = 0,.34; OR: 1.619 (1.098-2.386)]. Patients carrying "protector" genotype CC had higher probability of best corrected visual acuity improvement. When we analyzed VEGF A rs699947 polymorphism we found that patients expressing AA genotype had a higher chance of increasing their best corrected visual acuity [p:0,022; OR 1,532 (1,015-2,313)]. We did not find statistically significant differences reagarding VEGFR rs2071559 polymorphism and treatment response. CONCLUSIONS: Polymorphisms of VEGF A seem to influence the different response to antiangiogenic treatment in patients with AMD in our population, although further investigation is needed to know the mechanisms of this relationship.

Cistoid macular edema as first manifestation of sarcoidosis.

The purpose of this study is to report a case of cystoid macular edema (CME) as a rare first manifestation of ocular sarcoidosis after cataract surgery. A 60-year-old male developed a CME following uneventful phacoemulsification cataract extraction on his left eye. It resolved with conventional medical therapy. One year later the patient was diagnosed with bilateral CME. Oral corticosteroid therapy produced a significant regression. His medical and ocular histories were unremarkable and all tests for etiological diagnosis were negative. There were inflammation recurrences in his left eye, which were also treated with steroids. Optical coherence tomography showed complete resolution of foveal thickening without improvement in vision. Four years later, the patient presented with CME in both eyes. The laboratory tests included high angiotensin-converting enzyme levels and a gallium scan which were also consistent with sarcoidosis. Azathioprine was needed for management of ocular involvement, but it was withheld due to side-effects. At the present time, the CME is controlled with low-dose corticoids. Ocular involvement in sarcoidosis occurs in 20-50 % of patients. CME is not often the initial manifestation of the disease, but ocular sarcoidosis may present with a wide variety of ocular symptoms in all parts of the eye. Therefore, sarcoidosis should be kept in mind when evaluating a patient with ocular inflammation.