José A. Cristóbal

Finite element simulation of arcuates for astigmatism correction

In order to simulate the corneal incisions used to correct astigmatism, a three-dimensional finite element model was generated from a simplified geometry of the anterior half of the ocular globe. A hyperelastic constitutive behavior was assumed for cornea, limbus and sclera, which are collagenous materials with a fiber structure. Due to the preferred orientations of the collagen fibrils, corneal and limbal tissues were considered anisotropic, whereas the sclera was simplified to an isotropic one assuming that fibrils are randomly disposed. The reference configuration, which includes the initial strain distribution that balances the intraocular pressure, is obtained by an iterative process. Then the incisions are simulated. The final positions of the nodes belonging to the incised meridian and to the perpendicular one are fitted by both radii of curvature, which are used to calculate the optical power. The simulated incisions were those specified by Lindstroms nomogram [Chu, Y., Hardten, D., Lindquist, T., Lindstrom, R., 2005. Astigmatic keratotomy. Duanes Ophthalmology. Lippincott Williams and Wilkins, Philadelphia] to achieve 1.5, 2.25, 3.0, 4.5 and 6.0D of astigmatic change, using the next values for the parameters: length of 45 degrees , 60 degrees and 90 degrees , an optical zone of 6mm, single or paired incisions. The model gives results similar to those in Lindstroms nomogram [Chu et al., 2005] and can be considered a useful tool to plan and simulate refractive surgery by predicting the outcomes of different sorts of incisions and to optimize the values for the parameters involved: depth, length, position.

Retinal alterations in mild cognitive impairment and Alzheimer’s disease: an optical coherence tomography study

Retinal nerve fiber layer thickness (RNFL) measured by means of Optical Coherence Tomography (OCT) has been used as a marker not only of ophthalmologic diseases but also of neurodegenerative diseases such as Alzheimer’s disease (AD) and mild cognitive impairment (MCI). The purpose of this work was to demonstrate that patients with amnestic MCI show an intermediate RNFL thickness between normality and AD, and a macular volume and thickness as well. In a cross-sectional study we consecutively recruited 18 patients with AD, 21 with MCI, and 41 healthy controls. OCT was performed in all of them to measure circumpapillary RNFL thickness in µm, as well as macular volume and thickness. In the analysis of variance we saw that RNFL was thinner in MCI patients compared with controls, and it was also thinner in AD patients compared with MCI patients and controls. With regard to the macular measurements in mm3, MCI patients had the greatest macular volume in comparison with AD patients and controls. In turn the controls had greater macular volume than AD patients. The decreased RNFL thickness in MCI and AD patients suggests loss of retinal neurons and their axons. The increased thickness and macular volume have never been reported before in aMCI. This finding could be explained by inflammation and/or gliosis in early stages of AD. OCT could be a useful marker of AD for early detection and monitoring progression.

Evaluation of in vitro efficacy of combined riboflavin and ultraviolet a for Acanthamoeba isolates.

PURPOSE To evaluate in vitro the amoebicidal effects of riboflavin and ultraviolet A (UVA) collagen cross-linking. DESIGN Experimental study, laboratory investigation. METHODS Two different strains of Acanthamoeba species were tested identically. Four treatment groups were considered: group 1 consisted of 0.1% riboflavin and 30-minute UVA irradiation; group 2 consisted of 0.1% riboflavin and 60-minute UVA irradiation; group 3 consisted of no riboflavin and no UVA exposure; group 4 consisted of 0.1% riboflavin and no UVA exposure. The application of UVA was performed under the parameters used for in vivo corneal collagen cross-linking. RESULTS In all cases, cysts and trophozoites were detected 24 hours after treatment at a radial distance from the center of the seeding point more than 5 mm, indicating that the amoebae were viable. All treated and untreated groups of amoebae from the 2 strains exhibited growth (radii of 14 to 15 mm in groups 1, 3, and 4; radius of 12 mm in group 2). The final morphologic features of the 2 strains of trophozoites that received treatment were similar to those of the initial seeding group and the untreated control group. CONCLUSIONS The results obtained in our study show that a single dose (30 or 60 minutes) of cross-linking cannot achieve eradication in the 2 different Acanthamoeba strains examined. However, in vitro results do not always indicate in vivo efficacy, so future studies should test the validity of this treatment for Acanthamoeba keratitis.

Development of a prediction formula of Parkinson disease severity by optical coherence tomography

The aims of this study were to assess the peripapillary retinal nerve fiber layer (RNFL) thickness in patients with Parkinsons disease (PD), to determine its correlation with disease severity, and to define a simple biomarker for predicting clinical severity. One hundred two eyes from 52 patients affected by PD were compared with 97 eyes from 50 age‐comparable controls. In all patients, peripapillary RNFL thickness was measured by optical coherence tomography (OCT). We used the Unified Parkinsons Disease Rating Scale (UPDRS) total score and measured responses in the on medication state. Eyes from patients with PD had a statistically significant decrease in average peripapillary RNFL thickness compared with control eyes (P < 0.001). This reduction was observed in every quadrant (inferior, superior, nasal [P < 0.001], and temporal [P = 0.017]) in patients with PD. Furthermore, a strong inverse correlation was found between the PD severity measured according to the UPDRS score and the average peripapillary RNFL thickness (r = −0.615; P < 0.001) and PD duration (r = −0.303; P = 0.002). From these results, we defined a regression equation that predicts the UPDRS score from the above‐mentioned variables: UPDRS = 81.6 + 29.6 * log PD duration (years) − 0.6 * RFNL thickness (μm). We observed that, as the evolution and severity of PD progress, the peripapillary RNFL layer thickness, as evaluated by OCT, gradually diminishes. These results suggest that the average peripapillary RNFL thickness measured by OCT might be useful as a biomarker to detect the early onset and progression of PD.

Retinal nerve fiber layer thickness measured by optical coherence tomography in patients with schizophrenia: A short report

Background and Objectives: Our study aims to assess retinal nerve fiber layer (RNFL) thickness in patients affected by schizophrenia. Methods: Ten schizophrenic patients (mean age 39 +/- 13 years, best corrected visual acuity ≥ 20/20, refractive error between +/-2 diopters, and intraocular pressure <18 mmHg) were enrolled. They were compared with 10 age-matched controls. In all subjects, optic nerve head (ONH) measurements, peripapillary RNFL thickness, macular thickness and volume were measured by optical coherence tomography (OCT). Results: Schizophrenic patients showed an statistically significant reduction of the overall RNFL thickness (95+/-13 μm, range: 53-110) compared with those values observed in control eyes (103+/-8 μm, range: 88-119) (p = 0.047, Mann-Whitney U test). We also observed reduced peripapillary RNFL thickness in nasal quadrant in schizophrenic patients (75+/-17 μm, range: 41-111) when compared with controls (84+/-10 μm, range: 67-105) (p = 0.048, Mann-Whitney U test). The remaining peripapillary RNFL quadrants, macular thickness and volume did not reveal differences between both groups. No statistically significant differences were observed between the control group and schizophrenia patients with regard to ONH measurements, macular thickness and volume. Conclusions: Schizophrenia patients had a reduction of peripapillary RNFL thickness evaluated by OCT. To our knowledge, neither reduced RNFL thickness nor macular thickness and volume have been previously documented in patients diagnosed with schizophrenia. These findings suggest that neuronal degeneration could be present in the retina of schizophrenic patients as previously observed in neurodegenerative disorders.

An overview of nonparametric contributions to the problem of functional estimation from biased data

This paper presents an overview of nonparametric contributions to the literature on estimation problems when the observations are taken from weighted distributions. Many situations involving biased data in a very diverse range of contexts are considered, with emphasis being placed on the applications of smoothing techniques to estimate curves, such as density and regression functions. Some important problems encountered in semiparametric models are also analyzed.

Assessment of Corneal Biomechanical Properties and Intraocular Pressure in Myopic Spanish Healthy Population

Purpose. To examine biomechanical parameters of the cornea in myopic eyes and their relationship with the degree of myopia in a western healthy population. Methods. Corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann correlated intraocular pressure (IOP), and corneal compensated IOP (IOPcc) were measured using the ocular response analyzer (ORA) in 312 eyes of 177 Spanish subjects aged between 20 and 56 years. Refraction was expressed as spherical equivalent (SE), which ranged from 0 to −16.50 diopters (D) (mean: −3.88 ± 2.90 D). Subjects were divided into four groups according to their refractive status: group 1 or control group: emmetropia (−0.50 ≤ SE < 0.50); group 2: low myopia (−0.75 ≤ SE < 3.00 D); group 3: moderate myopia (−3.00 ≤ SE ≤ −6.00 D); and group 3: high myopia (SE greater than −6.00 D). We analyzed the relationship between corneal biomechanics measured with ORA and SE. Results. CH in the emmetropia, low myopia, moderate myopia, and high myopia groups was 11.13 ± 0.98, 11.49 ± 1.25, 10.52 ± 1.54, and 10.35 ± 1.33 mmHg, respectively. CH in the highly myopic group was significantly lower than that in the emmetropic group (P = 0.07) and low myopic group (P = 0.035); however, there were no differences with the moderate myopic group (P = 0.872). There were no statistically significant differences regarding IOP among the four groups (P > 0.05); nevertheless, IOPcc was significantly higher in the moderately myopic (15.47 ± 2.47 mmHg) and highly myopic (16.14 ± 2.59 mmHg) groups than in the emmetropia (15.15 ± 2.06 mmHg) and low myopia groups (14.53 ± 2.37 mmHg). No correlation between age and the measured parameters was found. CH and IOPcc were weakly but significantly correlated with SE (r = 0.171, P = 0.002 and r = −0.131, P = 0.021, resp.). Conclusions. Present study showed only a very weak, but significant, correlation between CH and refractive error, with CH being lower in both moderately and highly myopic eyes than that in the emmetropic and low myopic eyes. These changes in biomechanical properties of the cornea may have an impact on IOP measurement, increasing the risk of glaucoma.

Retinal nerve fiber layer and macular thickness in patients with schizophrenia: Influence of recent illness episodes.

Optical coherence tomography (OCT) has been recently used to investigate neuropsychiatric disorders. We aimed to study retinal OCT measures of patients with schizophrenia with respect to healthy controls, and to evaluate possible differences between recent illness episode (RIE) and non-recent illness episode (NRIE) patients. Thirty schizophrenia patients were classified as RIE (n=10) or NRIE (n=20), and compared with 30 matched controls. Statistical analyses included linear mixed-effects models to study the association between OCT measures and group membership. Multivariate models were used to control for potential confounders. In the adjusted linear mixed-effects regression model, patients had a significantly thinner retinal nerve fiber layer (RNFL) in overall measurements, and in the nasal, superior and inferior quadrants. Macular inner ring thickness and macular volume were also significantly smaller in patients than controls. Compared with controls, in the adjusted model only NRIE (but not RIE) patients had significantly reduced RNFL overall measures, superior RNFL, nasal RNFL, macular volume, and macular inner ring thickness. No significant correlation was found between illness duration and retinal measurements after controlling for age. In conclusion, retinal parameters observed using OCT in schizophrenia patients could be related to clinical status and merit attention as potential state biomarkers of the disorder.

Confidence bands in nonparametric regression with length biased data

In this paper we deduce a confidence bands construction for the nonparametric estimation of a regression curve from length biased data, where a result from Bickel and Rosenblatt (1973,The Annals of Statistics,1, 1071–1095) is adapted to this new situation. The construction also involves the estimation of the variance of the local linear estimator of the regression, where we use a finite sample modification in order to improve the performance of these confidence bands in the case of finite samples.

Visual field defects in pediatric patients on vigabatrin monotherapy

Vigabatrin (GVG) is an effective antiepileptic drug used for treating partial seizures in adults and children. Over the last years, an increasing number of articles have been published reporting visual field defects (VFD) associated with GVG therapy in adults. To date, however, only an small number of pediatric patients have been reported. This paper is a retrospective review of clinical review to evaluate the prevalence and features of VFD in pediatric patients on GVG monotherapy. Methods: Fifteen children, on GVG therapy in the Department of Child Neurology, underwent visual field examination by static threshold automated perimetry using the Humphrey Field Analyzer Program 30-2. The age of these patients ranged from 6 to 18 years (12.4 ± 3.6 years), 10 of them being male and five female. Results: Three patients (20%) on GVG monotherapy showed VFD. These consisted in localised, bilateral, and relatively symmetrical, nasal field loss, with relative preservation of the temporal field within the central 30° area.