Association between SNPs of Metalloproteinases and Prostaglandin F2α Receptor Genes and Latanoprost Response in Open-Angle Glaucoma.

PURPOSE: To determine whether single nucleotide polymorphisms (SNPs) of genes coding for matrix metalloproteinases (MMPs) and the prostaglandin F2α receptor gene (PTGFR) are related to a response to latanoprost in a white Spanish population of glaucomatous patients. DESIGN: Case-control study. PARTICIPANTS: One hundred twenty-four patients with open-angle glaucoma. METHODS: Genotyping was performed in 117 patients with primary open-angle glaucoma with a minimum treatment duration of 4 weeks. Candidate genes and individual polymorphisms were selected according to the effect on the mechanism of action of latanoprost. Multi-SNP haplotype analyses for associations also were tested. MAIN OUTCOME MEASURES: Diurnal intraocular pressure reduction and genotyping of the SNPs in the MMPs and PTGFR. RESULTS: The PTGFR SNPs were associated with positive (rs6686438, rs10786455) and negative (rs3753380, rs6672484, rs11578155) responses to latanoprost. Multiple testing found 2 genes, PTGFR and MMP-1, were related to refractoriness to latanoprost. CONCLUSIONS: The SNPs of the PTGFR and MMP-1 genes may determine the latanoprost response in a white European Spanish population. This study identified 5 SNPs related to the latanoprost response; 1 SNP, rs3753380, already has been associated with a poor response to latanoprost in a healthy Japanese population. Latanoprost is a commonly used antiglaucomatous drug, and increased knowledge of its mechanism of action will lead to advances in pharmacogenetics.

Polymorphisms in CYP1B1 gene and the risk of suffering Primary Open-Angle Glaucoma: Systematic review and meta-analysis.

PURPOSE: It had been reported that mutations in CYP1B1 gene probably play an important role in the pathogenesis of primary open angle glaucoma (POAG) but the existing genetic association studies show contradictory results. Thus, the objective of our study was to perform a systematic review and meta-analysis to characterize more precisely the potential association between given polymorphisms in CYP1B1 gene and the risk of suffering POAG. METHODS: A systematic review of studies that related the risk of carrying CYP1B1 gene polymorphisms with POAG development was conducted. We selected 19 case-control studies including 3855 POAG patients and 4125 control subjects in our meta-analyses. A random effects model was used. Sensitivity analysis and assessment of bias were also included. RESULTS: The prevalence of CYP1B1 gene polymorphisms were significantly more frequent among POAG patients compared to all controls (OR = 2.91, 95% CI = 1.37 - 6.21; P = 0.006). Moreover, their prevalence was significantly higher in juvenile-onset patients than in adult-onset ones (OR = 2.27, 95% CI = 1.20-4.28; P = 0.001). CONCLUSION: The results of this meta-analysis uphold that being a carrier of polymorphic genetic variants in CYP1B1 gene would increase the risk of POAG, especially the juvenile onset.

The parameters of the porcine eyeball.

BACKGROUND: The eye of the domestic pig (Sus scrofa domestica) is an ex vivo animal model often used in vision sciences research (retina studies, glaucoma, cataracts, etc.). However, only a few papers have compiled pig eye anatomical descriptions. The purpose of this paper is to describe pig and human eye anatomical parameters to help investigators in their choice of animal model depending on their study objective. METHODS: A wide search of current medical literature was performed (English language) using PubMed. Anteroposterior axial length and corneal radius, astigmatism, vertical and horizontal diameter, and pachymetry (slit-scan and ultrasound) were measured in five enucleated pig eyes of animals 6 to 8 months old. RESULTS: Horizontal corneal diameter was 14.31 ± 0.25 mm (CI 95% 14.03 mm-14.59 mm), vertical diameter was 12.00 ± 0 mm, anteroposterior length was 23.9 ± 0.08 mm (CI 95% 23.01 mm-29.99 mm), central corneal ultrasound pachymetry was 877.6 ± 13.58 µm (CI 95% 865.70 µm-889.50 µm) and slit-scan pachymetry was 906.2 ± 15.30 µm (CI 95% 892.78 µm-919.61 µm). Automatic keratometry (main meridians) was 41.19 ± 1.76D and 38.83 ± 2.89D (CI 95% 40.53D-41.81D and 37.76D-39.89D respectively) with an astigmatism of 2.36 ± 1.70D (CI 95% 1.72D-3.00D), and manual keratometry was 41.05 ± 0.54D and 39.30 ± 1.15D (CI 95% 40.57D-41.52D and 38.29D-40.31D respectively) with an astigmatism of 1.75 ± 1.31D (CI 95% 0.60D-2.90D). CONCLUSION: This paper describes the anatomy of the pig eyeball for easy use and interpretation by researchers who are considering their choice of animal model in vision sciences research.

Development of a new algorithm based on FDT Matrix perimetry and SD-OCT to improve early glaucoma detection in primary care.

PURPOSE: The purpose of this study was to develop an objective algorithm to discriminate the earliest stages of glaucoma using frequency doubling technology (FDT) Matrix perimetry and spectral domain-optical coherence tomography (OCT) technology to improve primary care detection. MATERIALS AND METHODS: Three hundred six eyes (mean age 58.67±15.12) from 161 patients were included and classified in the following three groups: 101 nonglaucoma (GI-NG), 100 glaucoma suspect (GII-SG), and 105 open-angle glaucoma (GIII-OAG). All participants underwent a visual field exploration using the Humphrey Matrix visual field instrument and retinal nerve fiber layer evaluation using the Topcon 3D OCT-2000. Pattern deviation plot was divided into 19 areas and five aggrupation or quadrants and ranked with a value between 0 and 4 according to its likelihood of normality, and differences among three groups were analyzed. Principal component analysis (PCA) was also used to extract the most notable features of FDT and OCT, and a logistic regression analysis was applied to obtain the classification rules. RESULTS: Only area numbers 7 and 12 and the central zone of FDT Matrix showed statistical differences (P<0.05) between GI-NG and GII-SG. The classification rules were estimated by the four PCA obtained from FDT Matrix and 3D OCT-2000 in a separate and combined use. Area under the receiver operating characteristic curve was 78.88% with FDT-PCA, 82.09% with OCT-PCA, and 94.27% with combined use of FDT and OCT-PCA to discriminate GI-NG and GII-SG. CONCLUSION: The predictive rules based on FDT-PCA or OCT-PCA provide a high sensitivity and specificity to detect the earliest stages of glaucoma and even better in combined use. These predictive rules may help the future development of software for FDT Matrix perimetry and 3D OCT-2000, which will greatly improve their diagnostic ability, making them useful in daily practice in a primary care setting.

Intraobserver and Interobserver Agreement of Structural and Functional Software Programs for Measuring Glaucoma Progression.

IMPORTANCE: It is important to evaluate intraobserver and interobserver agreement using visual field (VF) testing and optical coherence tomography (OCT) software in order to understand whether the use of this software is sufficient to detect glaucoma progression and to make decisions regarding its treatment. OBJECTIVE: To evaluate agreement in VF and OCT software among 5 glaucoma specialists. DESIGN, SETTING AND PARTICIPANTS: The printout pages from VF progression software and OCT progression software from 100 patients were randomized, and the 5 glaucoma specialists subjectively and independently evaluated them for glaucoma. Each image was classified as having no progression, questionable progression, or progression. The principal investigator classified the patients previously as without variability (normal) or with high variability among tests (difficult). Using both software, the specialists also evaluated whether the glaucoma damage had progressed and if treatment change was needed. One month later, the same observers reevaluated the patients in a different order to determine intraobserver reproducibility. MAIN OUTCOMES AND MEASURES: Intraobserver and interobserver agreement was estimated using κ statistics and Gwet second-order agreement coefficient. The agreement was compared with other factors. RESULTS: Of the 100 observed patients, half were male and all were white; the mean (SD) age was 69.7 (14.1) years. Intraobserver agreement was substantial to almost perfect for VF software (overall κ [95% CI], 0.59 [0.46-0.72] to 0.87 [0.79-0.96]) and similar for OCT software (overall κ [95% CI], 0.59 [0.46-0.71] to 0.85 [0.76-0.94]). Interobserver agreement among the 5 glaucoma specialists with the VF progression software was moderate (κ, 0.48; 95% CI, 0.41-0.55) and similar to OCT progression software (κ, 0.52; 95% CI, 0.44-0.59). Interobserver agreement was substantial in images classified as having no progression but only fair in those classified as having questionable glaucoma progression or glaucoma progression. Interobserver agreement was fair regarding questions about glaucoma progression (κ, 0.39; 95% CI, 0.32-0.48) and consideration about treatment changes (κ, 0.39; 95% CI, 0.32-0.48). The factors associated with agreement were the glaucoma stage and case difficulty. CONCLUSIONS AND RELEVANCE: There was substantial intraobserver agreement but moderate interobserver agreement among glaucoma specialists using 2 glaucoma progression software packages. These data suggest that these glaucoma progression software packages are insufficient to obtain high interobserver agreement in both devices except in patients with no progression. The low agreement regarding progression or treatment changes suggests that both software programs used in isolation are insufficient for decision making.

Prototype of a nanostructured sensing contact lens for noninvasive intraocular pressure monitoring.

PURPOSE: To present the application of a new sensor based on a flexible, highly piezoresistive, nanocomposite, all-organic bilayer (BL) adapted to a contact lens (CL) for non-invasive monitoring intraocular pressure (IOP). METHODS: A prototype of a sensing CL, adapted to a pig eyeball, was tested on different enucleated pig eyes. A rigid, gas-permeable CL was designed as a doughnut shape with a 3-mm hole, where the BL film-based sensor was incorporated. The sensor was a polycarbonate film coated with a polycrystalline layer of the highly piezoresistive molecular conductor ß-(ET)2I3, which can detect deformations caused by pressure changes of 1 mm Hg. The pig eyeballs were subjected to controlled-pressure variations (low-pressure transducer) to register the electrical resistance response of the CL sensor to pressure changes. Similarly, a CL sensor was designed according to the anatomic characteristics of the eye of a volunteer on the research team. RESULTS: A good correlation (r² = 0.99) was demonstrated between the sensing CL electrical response, and IOP (mm Hg) changes in pig eyes, with a sensitivity of 0.4 Ω/mm Hg. A human eye test also showed the high potential of this new sensor (IOP variations caused by eye massage, blinking, and eye movements were registered). CONCLUSIONS: A new nanostructured sensing CL for continuous monitoring of IOP was validated in an in vitro model (porcine eyeball) and in a human eye. This prototype has adequate sensitivity to continuously monitor IOP. This device will be useful for glaucoma diagnosis and treatment.

Patient persistence with first-line antiglaucomatous monotherapy.

PURPOSE: To identify the extent of persistence (period of time of continuous therapy with the drug prescribed) of glaucoma patients treated with prostaglandins (latanoprost, bimatoprost, or travoprost), or beta-blocker (timolol) monotherapy. METHODS: An observational retrospective study of a 24-month follow-up in 191 patients (from four centers) was done to identify the time elapsed until patients discontinued their antiglaucomatous treatment. The relevant information was extracted from patients' medical charts. A descriptive analysis, a Kaplan-Meier survival analysis, and a Cox regression model were used to determine which drug was associated with greater patient persistence and to detect variables significantly influencing persistence. RESULTS: Descriptive analysis and survival curves showed that after 24 months, latanoprost was associated with a higher persistence in glaucoma treatment than the alternative agents: 81.6% versus 22.9% for bimatoprost, 65.4% for travoprost, and 60.5% for timolol (P < 0.0001). Persistence was significantly influenced by the antiglaucoma agent used as monotherapy (with a six-fold higher risk of treatment discontinuation during the follow-up period due to receiving bimatoprost instead of latanoprost; P < 0.0001) and patient age (P = 0.001). Even though comorbidities could not be directly related to persistence, their occurrence was related to patient age. The main reasons for treatment discontinuation were lack of efficacy, development of intolerance and/or adverse events, which were significant in the bimatoprost group, 28.6% (P < 0.001) and 48.6% (P < 0.001), respectively. CONCLUSIONS: Latanoprost shows higher patient persistence compared with travoprost, bimatoprost, and timolol in routine clinical practice, and could lead to better control of intraocular pressure and lower associated economic costs.