Correlation between genetic and environmental risk factors for age-related macular degeneration in Brazilian patients.

PURPOSE: To analyze the correlations between age-related macular degeneration (AMD) and genetic and environmental risk factors for in a Brazilian population. DESIGN: Cross-sectional study with a control group. METHODS: We collected data on 236 participants 50 years of age or older (141 with AMD and 95 controls without the disease). Data was obtained using a questionnaire and included information on demographics, ocular and medical history, family history of AMD, lifestyle, and smoking and drinking habits. Genetic evaluations included direct sequencing for the LOC387715 (rs10490924) variant, as well as PCR and enzymatic digestion for the CFH Y402H (rs1061170) and HTRA1 (rs11200638) variants. We performed a risk assessment of environmental risk factors and genetic variants associated with AMD and determined correlations between AMD and the data collected using multiple linear regression analysis. RESULTS: Of the 141 AMD cases, 99 (70%) had advanced AMD in at least one eye (57% neovascular AMD and 13% geographic atrophy), and 42 (30%) had not-advanced AMD. Family history of AMD (OR: 6.58; 95% CI: 1.94-22.31), presence of cardiovascular disease (CVD) (OR: 2.39; 95% CI: 1.08-5.28), low physical activity level (OR: 1.39; 95% CI: 0.82-2.37), and high serum cholesterol (OR: 1.49; 95% CI: 0.84-2.65) were associated with an increased risk for AMD. There was a significant association between CVD and incidence of advanced AMD (OR: 2.29; 95% CI 0.81-6.44). The OR for the risk allele of the LOC387715 gene, the CFH gene and the HTRA1 gene were 2.21 (95% CI: 1.47-3.35), 2.27 (95% CI: 1.52-3.37), and 2.76 (95% CI: 1.89-4.03), respectively. In the stepwise multiple linear regression analyses, the HTRA1 and CFH risk alleles, family history of AMD, the LOC387715 risk allele, and CVD were associated with an increased risk of AMD for a total of 25.6% contribution to the AMD phenotype. CONCLUSIONS: The analysis correlating environmental and genetic risk factors such as family history of AMD, and CVD and the variants of HTRA1, CFH, and LOC387715 genes showed an expressive contribution for the development of AMD among this admixed population.

Discrimination Between Healthy Eyes and Those With Mild Glaucoma Damage Using Hemoglobin Measurements of the Optic Nerve Head.

PRCIS: The Laguna ONhE, a software that measures the hemoglobin (Hb) concentration of the optic nerve head (ONH) from fundus photographs, demonstrated good accuracy in discriminating healthy eyes from eyes with mild glaucoma. PURPOSE: The aim was to evaluate Hb concentration of the optic nerve to distinguish between healthy eyes and eyes with mild glaucoma. METHODS: Eyes from patients with mild primary open angle glaucoma (MD > -6 dB) (n=58) and from healthy subjects (n=64) were selected. Retinal nerve fiber layer thickness measurements of all eyes were acquired with optical coherence tomography. Optic disc photographs were also obtained, and the images were analyzed using the Laguna ONhE software, which measures the amount of Hb in 24 sectors of the ONH. The software also calculates the Glaucoma Discriminant Function (GDF), an index that expresses the chance of the ONH being compatible with glaucoma. Areas under the receiver operating characteristic curve and sensitivities at fixed specificities of 90% and 95% of each Laguna ONhE parameter were calculated. RESULTS: The mean retinal nerve fiber layer thickness and vertical cup/disc ratio of the control and glaucoma groups were 90.0±10.6 µm versus 66.28±9.85 µm ( P <0.001) and 0.5±0.09 versus 0.65±0.09 ( P <0.001), respectively. Total Hb (67.9±4.45 vs. 62.89±4.89, P <0.001) and GDF (11.57±15.34 vs. -27.67±20.94, P <0.001) were significantly higher in the control group. The Hb concentration was also significantly higher in 21 of the 24 sectors in the control group compared with the glaucoma group ( P <0.05). The GDF had the largest areas under the receiver operating characteristic curve (0.93), with 79.3% sensitivity at a fixed specificity of 95%. CONCLUSION: Measurements of optic nerve Hb concentration using a colorimetry photographic device demonstrated good accuracy in discriminating healthy eyes from eyes with mild glaucoma. Further studies are need to understand vascular factors implicated in the development of glaucoma.

Association of the CFH Y402H Polymorphism with the 1-Year Response of Exudative AMD to Intravitreal Anti-VEGF Treatment in the Brazilian Population.

AIM: Evidence of the relationship between the polymorphism of the complement factor H (CFH) gene at position 402 (Y402H) and the response to the treatment of wet AMD is controversial. The aim of this study was to compare the functional and morphological 1-year evolution of patients with exudative AMD treated with antivascular endothelial growth factor (VEGF) drugs with the CFH Y402H polymorphism in the Brazilian population. METHODS: Forty-six patients treated for wet AMD with bevacizumab or ranibizumab in a pro re nata regimen were included. The evolution of best-corrected visual acuity (BCVA) and central retinal thickness (CRT), and the number of injections over 1 year of follow-up were correlated with CFH genotypes. RESULTS: The analysis of variance for the difference between the BCVA denoted as logMAR (logarithm of the minimum angle of resolution) values showed an improvement at 1 year when compared to baseline (p = 0.039). Profile contrast analysis showed that this difference was significant only in the group without the C allele (p = 0.049), without significance in patients presenting with the risk allele (p = 0.241). CRT showed a mean reduction at 1 year compared to baseline (p < 0.001). Significant differences in the profile contrast test were found in the group without the C allele (p < 0.001) and in patients with the risk allele (p = 0.002). No difference was found in the number of injections among the different groups (p = 0.787). CONCLUSIONS: The presence of the risk allele of the Y402H polymorphism in the CFH gene was related to a less favorable evolution over 1 year in this sample of the Brazilian population with exudative AMD who were being treated with anti-VEGF drugs. In agreement with similar previous studies, this study concludes that the CFH risk genotypes may affect the disease response to treatment.

Association between IL1A and IL1B polymorphisms and primary open angle glaucoma in a Brazilian population.

Abstract: The aim of this study was to investigate the association of five polymorphisms in the IL1A and IL1B genes in Brazilian patients with primary open angle glaucoma (POAG). A case­control study, including 214 unrelated POAG patients and 187 healthy individuals, was conducted to evaluate the frequency of polymorphisms in the IL1A and IL1B genes. Ophthalmic evaluation was performed and genomic DNA was obtained from all participants. Five single nucleotide polymorphisms (SNPs): IL1A (­889C/T: rs1800587:C > T, +4845G/T:rs17561G>T) and IL1B (­31C/T:rs1143627:T > C, ­511C/T:rs16944C>T and +3954C/T:rs1143634:C > T) were genotyped through direct sequencing. The association of individual SNPs was tested using logistic regression. There was an association between the ­31C/T and ­511 C/T polymorphisms in the IL1B gene with POAG (p = 0.002 and p = 0.009, respectively). High linkage disequilibrium was observed between the ­31C/T and ­511C/T polymorphisms. The statistical analysis showed that the T/C haplotype (­31/­511) in the IL1B gene is more frequent in controls (p = 0.011) and the C/T haplotype (­31/­511) is more common in POAG patients (p = 0.018). Among POAG cases, the genotypic distribution of the ­31C/T and ­511 C/T SNPs was significantly different in patients who underwent anti-glaucomatous surgery compared to patients without surgery (p = 0.016 and 0.023, respectively). There was no statistically significant difference for the remaining SNPs between POAG patients and controls. In conclusion, the C allele of the ­31C/T and the T allele of the ­511C/T polymorphisms in the IL1B gene may represent a "risk haplotype" for the development of POAG in Brazilian individuals. Further studies with larger cohorts of patients are necessary to substantiate these findings.

Intra- and interobserver reproducibility of Bruch's membrane opening minimum rim width measurements with spectral domain optical coherence tomography.

PURPOSE: To investigate the reproducibility of Bruch's membrane opening minimum rim width (BMO-MRW) and retinal nerve fibre layer thickness (RNFLT) measurements using spectral domain optical coherence tomography (SD-OCT). Additionally, to investigate the reproducibility of BMO area measurements and fovea to BMO centre (FoBMO) angle. METHODS: Participants were healthy subjects (n = 30) and patients with glaucoma (n = 26). One eye of each participant was scanned to obtain optic nerve head (24 radial B-scans) and peripapillary (one circular B-scan) images by three independent examiners. Additionally, one examiner imaged each participant three times on the same day. Intra- and interobserver reproducibilities were estimated by within-subject standard deviation (SW) and coefficient of variation (COV). Spearman's rank correlation coefficient was used to test the correlation between the magnitude of the parameter and its standard deviation. RESULTS: The global BMO-MRW COVs (%) in healthy/glaucoma subjects were 0.87/1.34 and 1.28/3.13 for intra- and interobserver analyses, respectively, and the corresponding global RNFLT figures were 1.50/2.10 and 2.04/2.87. Global mean BMO-MRW and RNFLT showed no correlation with their respective standard deviations. The reproducibilities of BMO area and FoBMO angle were excellent and similar between the groups. CONCLUSION: The reproducibilities of BMO-MRW, BMO area measurements and FoBMO angle were excellent in both healthy subjects and patients with glaucoma. Bruch's membrane opening minimum rim width (BMO-MRW) reproducibility is comparable to that of RNFLT measurements.

Allogeneic Mesenchymal Stem Cell Transplantation in Dogs With Keratoconjunctivitis Sicca.

Keratoconjunctivitis sicca (KCS) is a dysfunction in tear production associated with clinical signs, which include conjunctival hyperemia, ocular discharge, discomfort, pain, and, eventually, corneal vascularization and pigmentation. Immunosuppressive drugs are routinely administrated for long periods to treat KCS but with side effects and limited results. Evaluation of the clinical benefits of intralacrimal transplantation of allogeneic mesenchymal stem cells (MSCs) in dogs with mild-moderate and severe KCS was done. A total of 24 eyes with KCS from 15 dogs of different breeds were enrolled in the present study. A single transplantation of MSCs (1 × 106) directly into lacrimal glands (dorsal and third eyelid) was performed. The Schirmer tear tests (STTs) and ocular surface improvements were used to assess short- and long-term effects of these cells. The STTs were carried out on day 0 (before MSCs transplantation) and on days 7, 14, 21, and 28, as well as 6 and 12 months after MSC transplantation. Our data demonstrate that allogeneic MSC transplantation in KCS dogs is safe since no adverse effects were observed immediately after transplantation and in short- and long-term follow-ups. A statistically significant increase in the STT and ocular surface improvements was found in all eyes studied. In all the eyes with mild-moderate KCS, STT values reverted to those of healthy eyes, while in eyes with severe KCS, although complete reversion was not found, there was improvement in tear production and in other clinical signs. Our study shows that a single dose of a low number of MSCs can be used to treat KCS in dogs. In contrast to immunosuppressive drug use, MSC transplantation has an effect over a long period (up to 12 months), even after a single administration, and does not require daily drug administration.

Pharmacogenetic Effect of Complement Factor H Gene Polymorphism in Response to the Initial Intravitreal Injection of Bevacizumab for Wet Age-Related Macular Degeneration.

PURPOSE: To compare the functional and morphological response to the initial intravitreal (IVT) injection of bevacizumab in exudative age-related macular degeneration (AMD) patients with the complement factor H (CFH) gene polymorphism T1277C in the Brazilian population. METHODS: Twenty-five unrelated patients with treatment-naive exudative AMD underwent an IVT injection of 1.25 mg bevacizumab at the initial presentation (D0) and were reexamined 7 days (D7) and 28 days (D28) later. The time and extent of visual acuity (VA) and central retinal thickness (CRT) changes were evaluated according to the presence of the T1277C polymorphism. RESULTS: In the homozygous risk group (CC), VA improvement was detected mostly from D7 to D28, while in the heterozygous (CT) and homozygous for the wild-type allele (TT) groups, functional response occurred earlier, from D0 to D7. Morphological response to the first IVT injection of bevacizumab was significant in the CT and TT groups, while the CC group presented no significant change in CRT up to D28. CONCLUSION: The CC variant of the CFH gene polymorphism T1277C is related to delayed functional and limited morphological response to the initial IVT injection of bevacizumab in exudative AMD patients in a sample of the Brazilian population.

Endophthalmitis caused by Agrobacterium radiobacter.

Infections due to Agrobacterium radiobacter are rare. This study reports 2 cases of A. radiobacter endophthalmitis. To the authors' knowledge, these are only the second and third reported cases of endophthalmitis caused by this Gram-negative rod.

Análise da técnica de instilaçäo de colírios por pacientes glaucomatosos / Analysis of the technique of instellation of drops by glaucoma patients

A falta de aderência ao tratamento é um problema de grandes proporçöes no glaucoma. Cem pacientes glaucomatosos em tratamento com colírios, foram submetidos a entrevistas que incluiam questöes sobre as medicaçöes antiglaucomatosas usadas. Os pacientes foram também solicitados a instilar um colírio da maneira a qual estavam acostumados. Dentre os 110 pacientes, 40 estavam sendo examinados pela primeira vez no Setor de Glaucoma (Casos Novos), enquanto 60 já estavam sendo acompanhados no mesmo Setor (Retornos). 77,50 (por cento) dos casos novos e 93,33 (por cento 1 dos retornos estavam usando colírio no momento da consulta (p=0,045). Apenas 2,5 (por cento) dos casos novos e 1,66 (por cento) dos retornos realizavam oclusäo do ponto lacrimal após a instilaçäo, enquanto 25 (por cento) dos casos novos e 23,3 (por cento) dos retornos instilavam col1rio no canto medial com ollho fechado. Este estudo demonstra que pacientes glaucomatosos, seguidos em um Hospital Universitário, näo tem recebido uma orientaçäo satisfatória quanto a dosagem e técnica de instilaçäo de colírios. Uma atençäo maior ao tema näo aderência poderia resultar em benefícios importantes na prevençäo da progressäo da lesäo glaucomatosa