Fernando Cruz-González

VEGF A (rs699947 and rs833061) and VEGFR2 (rs2071559) Gene Polymorphisms are not Associated with AMD Susceptibility in a Spanish Population

Abstract Purpose: Age-related macular degeneration (AMD) is a multifactorial disease due to interaction between genetic and environmental factors. Increased angiogenesis plays a central role in AMD development. Previous studies on the potential link between AMD and vascular endothelial growth factor (VEGFA) and vascular endothelial growth factor receptor (VEGFR) have yielded conflicting results. We have analysed if polymorphisms in genes coding for VEGFA and VEGFR are associated to susceptibility to suffer AMD in a cohort of Spanish subjects. Patients and Methods: We obtained peripheral blood samples from 151 patients with diagnosis of exudative AMD. We also studied 91 healthy subjects matched by age. We studied VEGFA rs699947 and rs833061, and VEGFR2 rs2071559 polymorphisms using real-time PCR with TaqMan probes. Results: We did not find statistically significant differences in genotypic distribution of VEGF rs699947 and rs833061 polymorphisms between patients and controls. However, analysis of VEGFR2 rs2071559 polymorphism shows that carriers of GG genotype are more frequent in subjects with AMD (p: 0.032; Odds Ratio(OR): 1.933; confidence interval (CI): 1.053–3.549), but, when corrected by Bonferroni testing, the result was found to be not significant. Conclusion: Our study shows that VEGFA rs699947 and rs833061 and VEGFR2 rs2071559 polymorphisms do not modify the risk of suffering AMD in a Spanish population.

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

Abstract 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.

CFH (rs1410996), HTRA1 (rs112000638) and ARMS2 (rs10490923) Gene Polymorphisms are Associated with AMD Risk in Spanish Patients

ABSTRACT Purpose: Age-related macular degeneration (AMD) is the main cause of legal blindness in the western adult population. We investigated the association between SNPs located in CFH, ARMS2 and HTRA1 and AMD in Spanish patients. Patients and Methods: We obtained peripheral blood samples from 121 patients with a diagnosis of AMD (84 exudative and 37 atrophic) at the Department of Ophthalmology of the University Hospital of Salamanca. We took 91 subjects as a control group. We studied a single nucleotide polymorphism (SNP) in each patient for each of the genes associated with high susceptibility to developing AMD using Real-time PCR with TaqMan probes for CFH and ARMS2 polymorphisms and PCR-RFLP for HTRA1 polymorphism. Results: We observed a statistically significant difference between patients and controls in the distribution of CFH rs1410996 genotypes, patients homozygous for the C-allele have twice the risk of developing the disease (p = 0.010; OR = 2,176 (1.194–3.964)). The analysis of ARMS2 rs10490923 polymorphism also showed differences in allelic distribution between the case and control groups (p < 0.001). Carriers of the T-allele appear more frequently in the group of patients (p < 0.001; OR = 3.340 (1.848–6.060)). Our results also confirm significant differences in the distribution of HTRA1 rs112000638 polymorphism with an increased representation of the G-allele in the patient’s group (p < 0.001; OR = 6.254(3.463–12.280)). Our study also indicates that TTGG ARMS2/HTRA1 (rs10490923/rs112000638) haplotype increases the risk of developing AMD by 9 times. Conclusions: Our results show that genotypes of ARMS2 (rs10490923), HTRA1 (rs112000638) and CFH (rs1410996) polymorphisms are related to an increased risk of suffering AMD in Spanish patients.

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.

Investigation of Association between Autophagy-Related Gene Polymorphisms and Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma in a Spanish Population

ABSTRACT Purpose: Cellular stress conditions are important mechanisms implicated in the pathogenesis of pseudoexfoliation syndrome. One of the potential cellular responses to these stress conditions is induction of autophagy. The purpose of this study was to evaluate whether genetic variants in three critical genes of autophagy (ATG16L, ATG2B, ATG5) may be involved in the development of pseudoexfoliation syndrome (XFS) and pseudoexfoliation glaucoma (XFG) in a Spanish population. Methods: 108 patients (64 XFS, 44XFG) and 118 healthy controls were evaluated. The analysis of genetic polymorphisms was performed by standard TaqMan allelic discrimination technique. Results: No significant differences in either genotype distributions or allelic frequencies of the tested polymorphisms were found between patients with XFS/XFG and control subjects. Conclusions: Our results suggest that these three genes that are critical components of the autophagy pathway (ATG16L, ATG2B, ATG5) are not significant risk factors among Spanish patients with either XFS or XFG.

Study of association between pre-senile cataracts and rs11615 of ERCC1, rs13181 of ERCC2, and rs25487 of XRCC1 polymorphisms in a Spanish population.

ABSTRACT Background: The purpose of this study was to attempt to determine if the presence of certain polymorphisms in the DNA repair genes (ERCC1, ERCC2, and XRCC1) is associated with pre-senile cataract development. Materials and methods: We performed a retrospective study over three groups of patients. The first group with pre-senile cataract was formed by 72 patients younger than 55 years with cataract surgery. The second group with senile cataract was formed by 101 patients older than 55 years with cataract surgery. And the third group, without cataract, was formed by 42 subjects older than 55 years without lens opacities. We analyzed the presence of SNP rs11615 from ERCC1, rs13181 from ERCC2, and rs25487 from XRCC1 and the relationship between risk factors such as smoking, alcohol intake, hypertension, and diabetes. Results: The comparison of the genotype distribution in ERCC1 and ERCC2 did not show any statistically significant association in any of our analyses (p > 0.05). The comparison of the genotype distribution in XRCC1 within the different groups did not show any statistically significant associations (p > 0.05), except for the comparison between the pre-senile cataract group and the group without cataract, where an increased risk of developing pre-senile cataract for the genotype Gln/Gln (p = 0.029; OR = 1.02–40.67) in recessive inheritance models was observed when adjusting for risk factors. Conclusions: Allelic variants in ERCC1 and ERCC2 are not associated with an increased risk of developing pre-senile cataract. The presence of Gln/Gln in XRCC1 in the pre-senile cataract group with regard to the group without cataract is associated with a major risk of developing pre-senile cataract.

Lesión macular bilateral tras la manipulación de un láser femtosegundo

CASE REPORT We describe the case of a 35-year-old man who arrived in the Emergency Department with bilateral macular injury caused by accidental exposure to an industrial femtosecond laser. DISCUSSION Workers operating industrial lasers must protect their eyes properly when handling these devices. Otherwise, retina damage may occur which usually is recoverable. However, sometimes this damage causes permanent visual loss.

Möbius Syndrome: Surgical Treatment for Eyelid Dysfunction

Introduction: Möbius syndrome is a heterogeneous congenital disorder that is linked to bilateral palsies of the cranial nerves VI and VII, resulting in congenital facial paralysis sometimes associated with impaired ocular abduction. Case Report: We present the case of a 44-year-old woman with Möbius syndrome and inferior recurrent keratitis secondary to scleral show in both eyes. We decided to use a cartilage graft from the ear in the inferior eyelid to avoid eyelid retraction and scleral show. Discussion: Patients with Möbius syndrome have a severe dysfunction of their facial mimic. Their treatment must be individualized, depending on their age, clinical examination and symptoms.