Tear metabolomics for the diagnosis of primary open-angle glaucoma.

Primary Open-Angle Glaucoma (POAG) is the most prevalent glaucoma type, and the leading cause of irreversible visual impairment and blindness worldwide. Identification of early POAG biomarkers is of enormous value, as there is not an effective treatment for the glaucomatous optic nerve degeneration (OND). In this pilot study, a metabolomic analysis, by using proton (1H) nuclear magnetic resonance (NMR) spectroscopy was conducted in tears, in order to determine the changes of specific metabolites in the initial glaucoma eyes and to discover potential diagnostic biomarkers. A classification model, based on the metabolomic fingerprint in tears was generated as a non-invasive tool to support the preclinical and clinical POAG diagnosis. 1H NMR spectra were acquired from 30 tear samples corresponding to the POAG group (n = 11) and the control group (n = 19). Data were analysed by multivariate statistics (partial least squares-discriminant analysis: PLS-DA) to determine a model capable of differentiating between groups. The whole data set was split into calibration (65%)/validation (35%), to test the performance and the ability for glaucoma discrimination. The calculated PLS-DA model showed an area under the curve (AUC) of 1, as well as a sensitivity of 100% and a specificity of 83.3% to distinguish POAG group versus control group tear data. This model included 11 metabolites, potential biomarkers of the disease. When comparing the study groups, a decrease in the tear concentration of phenylalanine, phenylacetate, leucine, n-acetylated compounds, formic acid, and uridine, was found in the POAG group. Moreover, an increase in the tear concentration of taurine, glycine, urea, glucose, and unsaturated fatty acids was observed in the POAG group. These results highlight the potential of tear metabolomics by 1H NMR spectroscopy as a non-invasive approach to support early POAG diagnosis and in order to prevent visual loss.

Automated macular choroidal thickness measurement by swept-source optical coherence tomography in pseudoxanthoma elasticum.

INTRODUCTION: Pseudoxanthoma elasticum (PXE) typically involves elastic fibers in blood vessels and Bruch membrane. Our purpose was to analyze retinal and choroidal macular thickness in patients with angioid streaks due PXE compared with a control group. METHODS: Best-corrected visual acuity (BCVA), axial length (AL), and macular swept-source optical coherence tomography were obtained. Automated segmentations of the retina and the choroid were used to obtain the corresponding thickness values. An age, gender and AL matched control group was used to compare the thickness values. RESULTS: Twelve eyes of 6 patients were included. The mean BCVA was 0.68 ± 0.29 versus 1.0 in controls (p < 0.001). The mean macular retinal thickness was thinner in eyes with PXE (p = 0.038). Only patients with choroidal neovascularization (NV) showed statistically significant differences in the mean macular choroidal thickness (p = 0.008). CONCLUSIONS: The present study shows that choroidal thickness may be thinner in eyes with NV due to angioid streaks in PXE compared with healthy eyes analyzed by an automated segmentation of the choroid. Further studies are warranted in order to assess the importance of this choroidal changes in the pathogenesis of retinal disturbances related to PXE and its influence in long-term follow-up.

Diagnostic Accuracy of Nonmydriatic Fundus Photography for the Detection of Glaucoma in Diabetic Patients.

PURPOSE: To determine the diagnostic accuracy for glaucoma of a set of criteria with nonmydriatic monoscopic fundus photography (NMFP) in diabetics. METHODS: Diabetics recruited from a screening program for diabetic retinopathy and diabetic glaucoma patients recruited from our glaucoma unit were included. Any patient with evidence of diabetic retinopathy was excluded. Diabetic patients had to have no visual field defects to be included as controls. Glaucoma patients had to have a glaucomatous field defect in at least one eye to be included. One NMFP was taken per eye for all subjects. These photographs were evaluated by two masked glaucoma specialists for the presence of the following: bilateral cup to disc (C/D) ratio ≥ 0.6, notching or thinning of the neuroretinal rim, disc hemorrhages, and asymmetry in the C/D ratio between both eyes ≥ 0.2. This evaluation led to a dichotomous classification: if any of the above criteria was present, the patient was classified as glaucoma. If none were present, the patient was classified as normal. RESULTS: 72 control subjects and 72 glaucoma patients were included. Evaluation of NMFP had a sensitivity of 79.17% and a specificity of 80.56% for specialist 1 and a sensitivity of 72.22% and a specificity of 88.88% for specialist 2 for the detection of glaucoma. The overall accuracy was 79.83% and 80.55%, respectively. DISCUSSION: NMFP evaluation by a glaucoma specialist may be useful for the detection of glaucoma in diabetics.

Intravitreal docosahexaenoic acid in a rabbit model: preclinical safety assessment.

PURPOSE: The purpose of the present study was to evaluate the retinal toxicity of a single dose of intravitreal docosahexaenoic acid (DHA) in rabbit eyes over a short-term period. METHODS: Sixteen New Zealand albino rabbits were selected for this pre-clinical study. Six concentrations of DHA (Brudy Laboratories, Barcelona, Spain) were prepared: 10 mg/50 µl, 5 mg/50 µl, 2'5 mg/50 µl, 50 µg/50 µl, 25 µg/50 µl, and 5 µg/50 µl. Each concentration was injected intravitreally in the right eye of two rabbits. As a control, the vehicle solution was injected in one eye of four animals. Retinal safety was studied by slit-lamp examination, and electroretinography. All the rabbits were euthanized one week after the intravitreal injection of DHA and the eyeballs were processed to morphologic and morphometric histological examination by light microscopy. At the same time aqueous and vitreous humor samples were taken to quantify the concentration of omega-3 acids by gas chromatography. Statistical analysis was performed by SPSS 21.0. RESULTS: Slit-lamp examination revealed an important inflammatory reaction on the anterior chamber of the rabbits injected with the higher concentrations of DHA (10 mg/50 µl, 5 mg/50 µl, 2'5 mg/50 µ) Lower concentrations showed no inflammation. Electroretinography and histological studies showed no significant difference between control and DHA-injected groups except for the group injected with 50 µg/50 µl. CONCLUSIONS: Our results indicate that administration of intravitreal DHA is safe in the albino rabbit model up to the maximum tolerated dose of 25 µg/50 µl. Further studies should be performed in order to evaluate the effect of intravitreal injection of DHA as a treatment, alone or in combination, of different retinal diseases.

Smoking and age-related macular degeneration: review and update.

Age-related macular degeneration (AMD) is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health.

Low thyroid hormone levels impair the perinatal development of the rat retina.

Eye development is regulated by multiple agents including hormones and growth factors. Thyroid hormone (triiodothyronine, or T(3), and the prohormone thyroxine, or T(4)) plays a crucial role in the development of the central nervous system. Here we have examined the effects of low T(3)/T(4) levels (hypothyroid status) on the developing rat retina during the perinatal stage. Eyes from control (CG) and T(3)/T(4)-deficient (HG) fetuses (E19 and E21) and newborn (P0, P3, P5 and P7) rats were obtained by administering a chemical antithyroid solution (0.02% methyl-mercaptoimidazole +1% ClOK(4)) in the tap water to the dams and their offspring, from E9 and throughout gestation until they were killed. Perinatal eyes were processed for light and electron transmission microscopy and subjected to morphological and morphometric analyses. Low T(3)/T(4) levels led to decreased retinal growth during the perinatal stage. In addition, the retinas from the HG presented fewer neuroblasts than those of their euthyroid counterparts (at E21: 705 +/- 83 cells per constant area of 4 x 10(4) microm(2) vs. 440 +/- 60 cells per constant area of 4 x 10(4) microm(2); p = 0.010). During development the index of mitosis in the retina peaked at E21, falling at the end of the 1st postnatal week. Significantly lower values were observed in the HG (at P5: 0.803 +/- 0.374 mitoses/cells % vs. 0.349 +/- 0.180 mitoses/cells %; p = 0.004). Furthermore, we have found that low T(3)/T(4) levels delayed and/or altered a series of developmental processes occurring in the retina during the perinatal stage such as layering and differentiation of several cell types. Our results demonstrate that thyroid hormone regulates rat neuroretinogenesis.

Ophthalmic involvement in the fetal alcohol syndrome: clinical and animal model studies.

The fetal alcohol syndrome (FAS) is caused by maternal alcohol misuse during pregnancy and is characterized by pre- and postnatal growth retardation, central nervous system anomalies and a wide spectrum of malformations, the most typical being the craniofacial features. The eye is a sensitive indicator of the adverse effects of environmental agents, and the ocular abnormalities observed in children with FAS indicate that the developing eye is particularly affected by alcohol. The external signs include short palpebral fissures, telecanthus, epicanthus, blepharoptosis, microphthalmos and strabismus. Within the eyes, the signs and symptoms most commonly detected are optic nerve hypoplasia, increased tortuosity of the retinal vessels and impaired vision. Experimental models of FAS, closely reproducing characteristics of human FAS, have contributed to our understanding of the cellular and molecular basis of the action of alcohol in the developing visual system. As there is such a high frequency of eye signs and symptoms in FAS, an ophthalmological examination is important when making the diagnosis, as well as in the management of the disorder. Current knowledge of ophthalmological involvement in FAS in humans is presented, as well as a review of findings using animal models specially designed for studying ocular developmental changes induced by alcohol.